The role of diurnal fluctuations in excitatory amino acid carrier 1 levels in post-ischemic hippocampal Zn2+ accumulation.
This study aimed to investigate whether time of day of an ischemic insult affects Zn2+ accumulation and neuronal injury and determine whether altered Zn2+ accumulation is modulated by EAAC1 diurnal fluctuation in the hippocampus in a mouse model of ischemic stroke. Mice subjected to transient global ischemia for 40 min at Zeitgeber time 18 (ZT18) (23:00) exhibited reduced Zn2+ accumulation and neuronal death in the hilar region of the hippocampus compared to those at ZT4 (09,00). The EAAC1 protein expression in the hippocampus was increased at ZT18 relative to ZT4. Intracerebroventricular injection of a non-selective exc...
Source: Experimental Neurology - November 27, 2020 Category: Neurology Authors: Aratake T, Higashi Y, Hamada T, Ueba Y, Shimizu T, Shimizu S, Yawata T, Ueba T, Saito M Tags: Exp Neurol Source Type: research

Genetic suppression of the dopamine D3 receptor in striatal D1 cells reduces the development of L-DOPA-induced dyskinesia.
Abstract Parkinson's Disease (PD) is symptomatically managed with L-DOPA but chronic use results in L-DOPA-induced dyskinesia (LID) characterized by abnormal involuntary movements (AIMs). In LID, dopamine D3 receptors (D3R) are upregulated on D1 receptor (D1R)-bearing medium spiny neurons where the can synergistically drive downstream signaling and motor behaviors. Despite evidence implying D1R-D3R cooperativity in LID, the dyskinesiogenic role of D3R has never been directly tested. To this end, we developed a specific cre-dependent microRNA (miRNA) to irreversibly prevent D3R upregulation in D1R striatal cells. D...
Source: Experimental Neurology - November 26, 2020 Category: Neurology Authors: Lanza K, Centner A, Coyle M, Del Priore I, Manfredsson FP, Bishop C Tags: Exp Neurol Source Type: research

Intra-arterial anti-oxidant power negatively correlates with white matter injury, and oxidative stress positively correlates with disability in daily activities.
Abstract Oxidative stress influences many kinds of diseases. Our hypothesis is that oxidative stress and antioxidant potentials correlate with cognitive function, activities of daily life and white matter injury. (UMIN-CTR R000016770) Thirty-two consecutive patients participated to this study after informed consent. A routine biochemical analysis, modified-Rankin Scale (m-RS), revised Hasegawa Dementia Scale (HDS-R), Mini-Mental State Examination (MMSE) and fluid-attenuated-inversion-recovery imaging (FLAIR) were performed before admission. Derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxi...
Source: Experimental Neurology - November 26, 2020 Category: Neurology Authors: Norihito Shimamura, Katagai T, Fujiwara N, Ueno K, Watanabe R, Fumoto T, Naraoka M, Ohkuma H Tags: Exp Neurol Source Type: research

The role of immune inflammation in aneurysmal subarachnoid hemorrhage.
Abstract Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease, which mainly caused by the rupture of an intracranial aneurysm. Clinical trials have demonstrated that cerebral vasospasm (CVS) is not the sole contributor to delayed cerebral ischemia (DCI) and poor outcomes in patients with aSAH. Currently, accumulating evidence suggests that early brain injury (EBI), which occurs within 72 h after the onset of aSAH, lays the foundation for subsequent pathophysiological changes and poor outcomes of patients. The pathological mechanisms of EBI mainly include increased intracranial pressure, oxidative s...
Source: Experimental Neurology - November 26, 2020 Category: Neurology Authors: Zeyu Zhang, Yuanjian Fang, Cameron Lenahan, Sheng Chen Tags: Exp Neurol Source Type: research

MFG-E8 attenuates inflammation in subarachnoid hemorrhage by driving microglial M2 polarization.
Abstract Increasing evidence suggests that microglial polarization plays an important role in the pathological processes of neuroinflammation following subarachnoid hemorrhage (SAH). Previous studies indicated that milk fat globule-epidermal growth factor-8 (MFG-E8) has potential anti-apoptotic and anti-inflammatory effects in cerebral ischemia. However, the effects of MFG-E8 on microglial polarization have not been evaluated after SAH. Therefore, the aim of this study was to explore the role of MFG-E8 in anti-inflammation, and its effects on microglial polarization following SAH. We established the SAH model via ...
Source: Experimental Neurology - November 24, 2020 Category: Neurology Authors: Gao Y, Tao T, Wu D, Zhuang Z, Lu Y, Wu L, Liu G, Zhou Y, Zhang D, Wang H, Dai W, Li W, Hang CH Tags: Exp Neurol Source Type: research

Neuroinflammation evoked by brain injury in a rat model of lacunar infarct.
Abstract Stroke is the leading cause of long-term, severe disability worldwide. Immediately after the stroke, endogenous inflammatory processes are upregulated, leading to the local neuroinflammation and the potentiation of brain tissue destruction. The innate immune response is triggered as early as 24 h post-brain ischemia, followed by adaptive immunity activation. Together these immune cells produce many inflammatory mediators, i.e., cytokines, growth factors, and chemokines. Our study examines the immune response components in the early stage of deep brain lacunar infarct in the rat brain, highly relevant to...
Source: Experimental Neurology - November 19, 2020 Category: Neurology Authors: Dabrowska S, Andrzejewska A, Kozlowska H, Strzemecki D, Janowski M, Lukomska B Tags: Exp Neurol Source Type: research

Microglia depletion increase brain injury after acute ischemic stroke in aged mice.
Abstract Microglia are one of the first responders to ischemic injury. Aged microglia acquire a senescent phenotype and produce more inflammatory cytokines after stroke. Depletion of microglia in young mice worsens post-ischemic damage by increasing inflammation. However, young mice do not have dysfunctional microglia. Hence, we hypothesized that depletion of microglia in older mice will contribute to improved early recovery after ischemic stroke injury. Aged (18-19 month) mice were fed with either control chow diet (CD) or PLX5622 chow diet (PLXD) for 21 days. On day 22, a 60-min middle cerebral artery occlus...
Source: Experimental Neurology - November 19, 2020 Category: Neurology Authors: Lee SM, Hudobenko J, McCullough LD, Chauhan A Tags: Exp Neurol Source Type: research

The spatiotemporal spread of cervical spinal cord contusion injury pathology revealed by 3D in-line phase contrast synchrotron X-ray microtomography.
Abstract Extensive structural changes occur within the spinal cord following traumatic injury. Acute tissue debris and necrotic tissue are broken down, proliferating local glia and infiltrating leukocytes remodel tissue biochemical and biophysical properties, and a chronic cavity surrounded by a scar forms at the injury epicentre. Serial-section 2D histology has traditionally assessed these features in experimental models of spinal cord injury (SCI) to measure the extent of tissue pathology and evaluate efficacy of novel therapies. However, this 2D snapshot approach overlooks slice intervening features, with accur...
Source: Experimental Neurology - November 18, 2020 Category: Neurology Authors: Strotton MC, Bodey AJ, Wanelik K, Hobbs C, Rau C, Bradbury EJ Tags: Exp Neurol Source Type: research

Inhibition of the BCL6/miR-31/PKD1 axis attenuates oxidative stress-induced neuronal damage.
Abstract Ischemic stroke (IS) is one of the most common cerebrovascular diseases worldwide. The aberrant expression of BCL6 has been previously implicated in the pathogenesis of IS. Meanwhile, miR-31 is known as a target of BCL6, and has also been suggested to diminish cell damage by suppressing the PKD1 expression. Expanding on this relationship, the current study set out to investigate whether BCL6 participates in ischemic stroke by targeting PKD1. Firstly, IS models were established in vitro and in vivo. TUNEL staining and MTT assay were performed to examine the apoptosis and cell survival. In addition, qRT-PCR...
Source: Experimental Neurology - November 12, 2020 Category: Neurology Authors: Wei P, Chen H, Lin B, Du T, Liu G, He J, You C Tags: Exp Neurol Source Type: research

Traumatic brain injury modifies synaptic plasticity in newly-generated granule cells of the adult hippocampus.
This study investigated changes in long-term potentiation (LTP) within the DG in relation to TBI-induced neurogenesis. Adult male rats received a moderate TBI or sham injury and were sacrificed for brain slice recordings at 30 or 60 days post-injury. Recordings were taken from the medial perforant path input to DG granule cells in the presence or absence of the GABAergic antagonist picrotoxin, reflecting activity of either all DG granule cells or predominately newborn granule cells, respectively. Measurements of LTP observed in the total granule cell population (with picrotoxin) showed a prolonged impairment which worsen...
Source: Experimental Neurology - November 11, 2020 Category: Neurology Authors: Weston NM, Rolfe AT, Freelin AH, Reeves TM, Sun D Tags: Exp Neurol Source Type: research

From inflammasome to Parkinson's disease: Does the NLRP3 inflammasome facilitate exosome secretion and exosomal alpha-synuclein transmission in Parkinson's disease?
Abstract A pivotal neuropathological manifestation of synucleinopathies, like Parkinson's disease (PD), is the aggregation of α-synuclein. In a recent cell-to-cell transmission model of α-synuclein, α-synuclein propagation was demonstrated to resemble that of prion proteins in the central nervous system. Furthermore, exosomes, as biomolecule carriers, have been shown to transmit α-synuclein from neuron to neuron. However, the mechanisms underlying exosomal α-synuclein transmission have not been well understood. The NLR family pyrin domain containing 3 protein (NLRP3) inflammasome acti...
Source: Experimental Neurology - November 5, 2020 Category: Neurology Authors: Si XL, Fang YJ, Li LF, Gu LY, Yin XZ, Jun-Tian, Yan YP, Pu JL, Zhang BR Tags: Exp Neurol Source Type: research

Abolishing UCHL1's hydrolase activity exacerbates TBI-induced axonal injury and neuronal death in mice.
Abstract Ubiquitin (Ub) C-terminal hydrolase L1 (UCHL1) is a multifunctional protein that is expressed in neurons throughout brain at high levels. UCHL1 deletion is associated with axonal degeneration, progressive sensory motor ataxia, and premature death in mice. UCHL1 has been hypothesized to play a role in the pathogenesis of neurodegenerative diseases and recovery after neuronal injury. UCHL1 hydrolyzes Ub from polyubiquitinated (poly-Ub) proteins, but also may ligate Ub to select neuronal proteins, and interacts with cytoskeletal proteins. These and other mechanisms have been hypothesized to underlie UCHL1's ...
Source: Experimental Neurology - November 4, 2020 Category: Neurology Authors: Mi Z, Liu H, Rose ME, Ma X, Reay DP, Ma J, Henchir J, Dixon CE, Graham SH Tags: Exp Neurol Source Type: research

Genes causing congenital hydrocephalus: Their chromosomal characteristics of telomere proximity and DNA compositions.
Abstract Congenital hydrocephalus (CH) is caused by genetic mutations, but whether factors impacting human genetic mutations are disease-specific remains elusive. Given two factors associated with high mutation rates, we reviewed how many disease-susceptible genes match with (i) proximity to telomeres or (ii) high adenine and thymine (A + T) content in human CH as compared to other disorders of the central nervous system (CNS). We extracted genomic information using a genome data viewer. Importantly, 98 of 108 genes causing CH satisfied (i) or (ii), resulting in>90% matching rate. However, such a high accor...
Source: Experimental Neurology - November 3, 2020 Category: Neurology Authors: McKnight I, Hart C, Park IH, Shim JW Tags: Exp Neurol Source Type: research

The opportunities and challenges of machine learning in the acute care setting for precision prevention of posttraumatic stress sequelae.
Abstract Personalized medicine is among the most exciting innovations in recent clinical research, offering the opportunity for tailored screening and management at the individual level. Biomarker-enriched clinical trials have shown increased efficiency and informativeness in cancer research due to the selective exclusion of patients unlikely to benefit. In acute stress situations, clinically significant decisions are often made in time-sensitive manners and providers may be pressed to make decisions based on abbreviated clinical assessments. Up to 30% of trauma survivors admitted to the Emergency Department (ED) ...
Source: Experimental Neurology - November 3, 2020 Category: Neurology Authors: Schultebraucks K, Chang BP Tags: Exp Neurol Source Type: research

Preclinical neurorehabilitation with environmental enrichment confers cognitive and histological benefits in a model of pediatric asphyxial cardiac arrest.
Abstract Pediatric asphyxial cardiac arrest (ACA) often leaves children with physical, cognitive, and emotional disabilities that affect overall quality of life, yet rehabilitation is neither routinely nor systematically provided. Environmental enrichment (EE) is considered a preclinical model of neurorehabilitation and thus we sought to investigate its efficacy in our established model of pediatric ACA. Male Sprague-Dawley rat pups (post-natal day 16-18) were randomly assigned to ACA (9.5 min) or Sham injury. After resuscitation, the rats were assigned to 21 days of EE or standard (STD) housing during which t...
Source: Experimental Neurology - November 2, 2020 Category: Neurology Authors: Manole MD, Hook M, Nicholas M, Nelson BP, Liu A, Stezoski Q, Rowley A, Cheng JP, Alexander H, Moschonas EH, Bondi CO, Kline AE Tags: Exp Neurol Source Type: research

Emerging neuroprotective strategies for the treatment of ischemic stroke: An overview of clinical and preclinical studies.
Abstract Stroke is the leading cause of disability and the second leading cause of death worldwide. With the global population aged 65 and over growing faster than all other age groups, the incidence of stroke is also increasing. In addition, there is a shift in the overall stroke burden towards younger age groups, particularly in low and middle-income countries. Stroke in most cases is caused due to an abrupt blockage of an artery (ischemic stroke), but in some instances stroke may be caused due to bleeding into brain tissue when a blood vessel ruptures (hemorrhagic stroke). Although treatment options for stroke ...
Source: Experimental Neurology - October 31, 2020 Category: Neurology Authors: Paul S, Candelario-Jalil E Tags: Exp Neurol Source Type: research

Role of lipocalin-2 in extracellular peroxiredoxin 2-induced brain swelling, inflammation and neuronal death.
This study examined the role of LCN-2 in PRX-2 induced brain injury and involved three parts. In the first part, adult male C57BL/6 wild-type (WT), LCN-2 heterozygous (LCN-2 HET), and LCN-2 knockout (LCN-2 KO) mice received either an intracaudate injection of recombinant PRX-2 or saline. In the second part, adult male C57BL/6 WT and male LCN-2 KO mice received recombinant PRX-2 with either recombinant mouse LCN-2 protein or control. In the third part, adult female C57BL/6 WT, LCN-2 HET, and LCN-2 KO mice received recombinant PRX-2. Behavioral tests, and T2- and T2*- weighted magnetic resonance imaging was obtained for all ...
Source: Experimental Neurology - October 29, 2020 Category: Neurology Authors: Zhang J, Novakovic N, Hua Y, Keep RF, Xi G Tags: Exp Neurol Source Type: research

Neuroplasticity of the visual cortex: in sickness and in health.
Abstract Brain plasticity refers to the ability of synaptic connections to adapt their function and structure in response to experience, including environmental changes, sensory deprivation and injuries. Plasticity is a distinctive, but not exclusive, property of the developing nervous system. This review introduces the concept of neuroplasticity and describes classic paradigms to illustrate cellular and molecular mechanisms underlying synapse modifiability. Then, we summarize a growing number of studies showing that the adult cerebral cortex retains a significant degree of plasticity highlighting how the identifi...
Source: Experimental Neurology - October 24, 2020 Category: Neurology Authors: Baroncelli L, Lunghi C Tags: Exp Neurol Source Type: research

Alpha adrenergic receptor signaling in the hypothalamic paraventricular nucleus is diminished by the chronic intermittent hypoxia model of sleep apnea.
Abstract Chronic intermittent hypoxia (CIH) is a model for obstructive sleep apnea. The paraventricular nucleus (PVN) of the hypothalamus has been suggested to contribute to CIH-induced exaggerated cardiorespiratory reflexes, sympathoexcitation and hypertension. This may occur, in part, via activation of the dense catecholaminergic projections to the PVN that originate in the brainstem. However, the contribution of norepinephrine (NE) and activation of its alpha-adrenergic receptors (α-ARs) in the PVN after CIH exposure is unknown. We hypothesized CIH would increase the contribution of catecholaminergic inpu...
Source: Experimental Neurology - October 23, 2020 Category: Neurology Authors: Domingos-Souza G, Martinez D, Sinkler S, Heesch CM, Kline DD Tags: Exp Neurol Source Type: research

Phosphorylation of STAT3 by axonal Cdk5 promotes axonal regeneration by modulating mitochondrial activity.
Abstract Cyclin-dependent kinase 5 (Cdk5) is involved in neural organization and synaptic functions in developing and adult brains, yet its role in axonal regeneration is not known well. Here, we characterize Cdk5 function for axonal regeneration after peripheral nerve injury. Levels of Cdk5 and p25 were elevated in sciatic nerve axons after injury. Cdk5 activity was concomitantly induced from injured nerve and increased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) on the serine 727 residue. Pharmacological and genetic blockades of Cdk5 activity phosphorylating STAT3 resulted i...
Source: Experimental Neurology - October 21, 2020 Category: Neurology Authors: Hwang J, Namgung U Tags: Exp Neurol Source Type: research

The actin binding protein α-actinin-2 expression is associated with dendritic spine plasticity and migrating granule cells in the rat dentate gyrus following pilocarpine-induced seizures.
We examined the levels of α-actn-2 expression within the dentate gyrus (DG) during the development of chronic limbic seizures (epileptogenesis) induced by pilocarpine in rats. In this model, plasticity of the DG glutamatergic granule cells including spine loss, spinogenesis, morphogenesis, neo-synaptogenesis, aberrant migration, and alterations of NMDA receptors have been well characterized. We showed that α-actn-2 immunolabeling was reduced in the inner molecular layer at 1-2 weeks post-status epilepticus (SE), when granule cell spinogenesis and morphogenesis occur. This low level persisted at the chronic stag...
Source: Experimental Neurology - October 21, 2020 Category: Neurology Authors: Sbai O, Soussi R, Bole A, Khrestchatisky M, Esclapez M, Ferhat L Tags: Exp Neurol Source Type: research

Using routine MRI data of depressed patients to predict individual responses to electroconvulsive therapy.
j M Abstract Electroconvulsive therapy (ECT) is one of the most effective treatments in cases of severe and treatment resistant major depression. 60-80% of patients respond to ECT, but the procedure is demanding and robust prediction of ECT responses would be of great clinical value. Predictions based on neuroimaging data have recently come into focus, but still face methodological and practical limitations that are hampering the translation into clinical practice. In this retrospective study, we investigated the feasibility of ECT response prediction using structural magnetic resonance imaging (sMRI) data that wa...
Source: Experimental Neurology - October 14, 2020 Category: Neurology Authors: Gärtner M, Ghisu E, Herrera-Melendez AL, Koslowski M, Aust S, Asbach P, Otte C, Regen F, Heuser I, Borgwardt K, Grimm S, Bajbouj M Tags: Exp Neurol Source Type: research

N-acetylcysteine reduces brain injury after delayed hypoxemia following traumatic brain injury.
Abstract Preclinical investigations into neuroprotective agents for traumatic brain injury (TBI) have shown promise when administered before or very early after experimental TBI. However clinical trials of therapeutics demonstrating preclinical efficacy for TBI have failed to replicate these results in humans, a lost in translation phenomenon. N-acetylcysteine (NAC) is a potent anti-oxidant with demonstrated efficacy in pre-clinical TBI when administered early after primary injury. Utilizing our clinically relevant mouse model, we hypothesized that NAC administration in a clinically relevant timeframe could improv...
Source: Experimental Neurology - October 13, 2020 Category: Neurology Authors: Celorrio M, Rhodes J, Vadivelu S, Davies M, Friess SH Tags: Exp Neurol Source Type: research

TREM2 overexpression rescues cognitive deficits in APP/PS1 transgenic mice by reducing neuroinflammation via the JAK/STAT/SOCS signaling pathway.
In this study, to further explore the precise effects of TREM2 on neuroinflammation and the underlying mechanisms in AD, we employed a lentiviral-mediated strategy to overexpress TREM2 in the brain of APPswe/PS1dE9 (APP/PS1) transgenic mice and cultured BV2 cells. Our results showed that TREM2 overexpression rescued cognitive deficits, decreased β-amyloid (Aβ) plaques deposition, reduced synaptic and neuronal loss, as well as ameliorated neuroinflammation. The mechanistic study revealed that these protective effects were likely attributed to inhibition of neuroinflammatory responses through the JAK/STAT/SOCS sign...
Source: Experimental Neurology - October 13, 2020 Category: Neurology Authors: Ruganzu JB, Zheng Q, Wu X, He Y, Peng X, Jin H, Zhou J, Ma R, Ji S, Ma Y, Qian Y, Wang Y, Yang W Tags: Exp Neurol Source Type: research

CNS and peripheral immunity in cerebral ischemia: partition and interaction.
Abstract Stroke elicits excessive immune activation in the injured brain tissue. This well-recognized neural inflammation in the brain is not just an intrinsic organ response but also a result of additional intricate interactions between infiltrating peripheral immune cells and the resident immune cells in the affected areas. Given that there is a finite number of immune cells in the organism at the time of stroke, the partitioned immune systems of the CNS and periphery must appropriately distribute the limited pool of immune cells between the two domains, mounting a necessary post-stroke inflammatory response by ...
Source: Experimental Neurology - October 13, 2020 Category: Neurology Authors: Kim E, Cho S Tags: Exp Neurol Source Type: research

Alternative splicing of neurexins 1-3 is modulated by neuroinflammation in the prefrontal cortex of a murine model of multiple sclerosis.
Abstract Mounting evidence points to immune-mediated synaptopathy and impaired plasticity as early pathogenic events underlying cognitive decline (CD) in Multiple sclerosis (MS) and in the experimental autoimmune encephalopathy (EAE) mouse model of the disease. However, knowledge of the neurobiology of synaptic dysfunction is still incomplete. Splicing regulation represents a flexible and powerful mechanism involved in dynamic remodeling of the synapse, which allows the expression of synaptic protein variants that dynamically control the specificity of contacts between neurons. The pre-synaptic adhesion molecules ...
Source: Experimental Neurology - October 12, 2020 Category: Neurology Authors: Marchese E, Valentini M, Sante GD, Cesari E, Adinolfi A, Corvino V, Ria F, Sette C, Geloso MC Tags: Exp Neurol Source Type: research

INT-777 prevents cognitive impairment through activating Takeda G protein-coupled receptor 5 (TGR5) by attenuating neuroinflammation via cAMP/ PKA/ CREB signaling axis in a rat model of sepsis.
CONCLUSION: This study demonstrates that INT-777 treatment reduced neuroinflammation and microglial cell activation, but improved cognitive impairment in the experimental sepsis rats. TGR5 has translational potential as a therapeutic target to improve neurological outcomes in sepsis survivors. PMID: 33058889 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - October 12, 2020 Category: Neurology Authors: Jin P, Deng S, Tian M, Lenahan C, Wei P, Wang Y, Tan J, Wen H, Zhao F, Gao Y, Gong Y Tags: Exp Neurol Source Type: research

Hemizygous deletion of Tbk1 worsens neuromuscular junction pathology in TDP-43G298S transgenic mice.
Abstract Mutations in the genes TARDBP (encoding the TDP-43 protein) and TBK1 can cause familial ALS. Neuronal cytoplasmatic accumulations of the misfolded, hyperphosphorylated RNA-binding protein TDP-43 are the pathological hallmark of most ALS cases and have been suggested to be a key aspect of ALS pathogenesis. Pharmacological induction of autophagy has been shown to reduce mutant TDP-43 aggregates and alleviate motor deficits in mice. TBK1 is exemplary for several other ALS genes that regulate autophagy. Consequently, we employed double mutant mice with both a heterozygous Tbk1 deletion and transgenic expressi...
Source: Experimental Neurology - October 7, 2020 Category: Neurology Authors: Sieverding K, Ulmer J, Bruno C, Satoh T, Tsao W, Freischmidt A, Akira S, Wong PC, Ludolph AC, Danzer KM, Lobsiger CS, Brenner D, Weishaupt JH Tags: Exp Neurol Source Type: research

NPD1 rapidly targets mitochondria-mediated apoptosis after acute injection protecting brain against ischemic injury.
Abstract Mitochondria-related cell death pathways play a major role in ischemic brain injury. Thus, mitochondrial "protective" molecules could be considered for new therapeutic regimens. We recently reported that acute administration of docosahexaenoic acid (DHA) triglyceride lipid emulsion, immediately after hypoxic-ischemic (HI) insult, markedly attenuated brain infarct size. This was associated with an early change of DHA-derived specialized pro-resolving mediator (SPM) profiles. Specifically, DHA treatment induced a 50% increase of neuroprotectin D1 (NPD1) levels in ischemic brain. Based on these fin...
Source: Experimental Neurology - October 7, 2020 Category: Neurology Authors: Zirpoli H, Sosunov SA, Niatsetskaya ZV, Mayurasakorn K, Kollareth DJM, Serhan CN, Ten VS, Deckelbaum RJ Tags: Exp Neurol Source Type: research

Impact of aging and comorbidities on ischemic stroke outcomes in preclinical animal models: A translational perspective.
Abstract Ischemic stroke is a highly complex and devastating neurological disease. The sudden loss of blood flow to a brain region due to an ischemic insult leads to severe damage to that area resulting in the formation of an infarcted tissue, also known as the ischemic core. This is surrounded by the peri-infarct region or penumbra that denotes the functionally impaired but potentially salvageable tissue. Thus, the penumbral tissue is the main target for the development of neuroprotective strategies to minimize the extent of ischemic brain damage by timely therapeutic intervention. Given the limitations of reperf...
Source: Experimental Neurology - October 6, 2020 Category: Neurology Authors: Candelario-Jalil E, Paul S Tags: Exp Neurol Source Type: research

Lesions of the nucleus basalis magnocellularis (Meynert) induce enhanced somatosensory responses and tactile hypersensitivity in rats.
Abstract We used the immunotoxin 192 immunoglobulin G-saporin to produce a selective cholinergic lesion in the nucleus basalis of Meynert (NBM) of rats and investigated whether the NBM lesion led to tactile hypersensitivity in the forepaw. The paw mechanical threshold test showed that the lesioned rats had a decreased threshold compared to the control. Surprisingly, there was a significant positive correlation between mechanical threshold and survival rate of NBM cholinergic neurons. Furthermore, using local field potential (LFP) recordings and voltage-sensitive dye (VSD) imaging, we found that the forepaw-evoked ...
Source: Experimental Neurology - September 30, 2020 Category: Neurology Authors: Dezawa S, Nagasaka K, Watanabe Y, Takashima I Tags: Exp Neurol Source Type: research

SIRT1 mediates hypoxic preconditioning induced attenuation of neurovascular dysfunction following subarachnoid hemorrhage.
CONCLUSION: SIRT1 mediates hypoxic preconditioning-induced protection against neurovascular dysfunction after SAH. Resveratrol mimics this neurovascular protection, at least in part, via SIRT1. Activation of SIRT1 is a promising, novel, pleiotropic therapeutic strategy to combat DCI after SAH. PMID: 33010255 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - September 29, 2020 Category: Neurology Authors: Vellimana AK, Aum DJ, Diwan D, Clarke J, Nelson JW, Lawrence M, Han BH, Gidday JM, Zipfel GJ Tags: Exp Neurol Source Type: research

Seizure burden fluctuates with the female reproductive cycle in a mouse model of chronic temporal lobe epilepsy.
Abstract Women with catamenial epilepsy often experience increased seizure burden near the time of ovulation (periovulatory) or menstruation (perimenstrual). To date, a rodent model of chronic temporal lobe epilepsy (TLE) that exhibits similar endogenous fluctuations in seizures has not been identified. Here, we investigated whether seizure burden changes with the estrous cycle in the intrahippocampal kainic acid (IHKA) mouse model of TLE. Adult female IHKA mice and saline-injected controls were implanted with EEG electrodes in the ipsilateral hippocampus. At one and two months post-injection, 24/7 video-EEG recor...
Source: Experimental Neurology - September 28, 2020 Category: Neurology Authors: Li J, Leverton LK, Naganatanahalli LM, Christian-Hinman CA Tags: Exp Neurol Source Type: research

Small molecule modulation of the p75 neurotrophin receptor suppresses age- and genotype-associated neurodegeneration in HIV gp120 transgenic mice.
Abstract The persistence of HIV in the central nervous system leads to cognitive deficits in up to 50% of people living with HIV even with systemic suppression by antiretroviral treatment. The interaction of chronic inflammation with age-associated degeneration places these individuals at increased risk of accelerated aging and other neurodegenerative diseases and no treatments are available that effectively halt these processes. The adverse effects of aging and inflammation may be mediated, in part, by an increase in the expression of the p75 neurotrophin receptor (p75NTR) which shifts the balance of neurotrophin...
Source: Experimental Neurology - September 28, 2020 Category: Neurology Authors: Xie Y, Seawell J, Boesch E, Allen L, Suchy A, Longo FM, Meeker RB Tags: Exp Neurol Source Type: research

Introduction to spasticity and related mouse models.
t M Abstract Although spasticity is one of the most common causes of motor disability worldwide, its precise definition and pathophysiology remain elusive, which to date renders its experimental targeting tricky. At least in part, this difficulty is caused by heterogeneous phenotypes of spasticity-causing neurological disorders, all causing spasticity by involving upper motor neurons. The most common clinical symptoms are a series of rapid muscle contractions (clonus), an increased muscle tone (hypertonia), and augmented tendon reflex activity (hyperreflexia). This muscle overactivity is due to disturbed inhibitio...
Source: Experimental Neurology - September 28, 2020 Category: Neurology Authors: Wieters F, Lucas CW, Gruhn M, Büschges A, Fink GR, Aswendt M Tags: Exp Neurol Source Type: research

Interaction of human IAPP and A β1-42 aggravated the AD-related pathology and impaired the cognition in mice.
Interaction of human IAPP and Aβ1-42 aggravated the AD-related pathology and impaired the cognition in mice. Exp Neurol. 2020 Sep 29;:113490 Authors: Chen HC, Cao JX, Cai YT, Du HL, Xi XX, Sun J, Yin J, Gao LP, Jing YH Abstract Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) have a common pathology. Both diseases are characterized by local deposition of amyloid proteins in the brain or islet organ, but their phenotypes and clinical manifestation vary widely. Although the sources of islet amyloid polypeptide (IAPP) and amyloid beta (Aβ) are independent, their fibrillar sequences ...
Source: Experimental Neurology - September 28, 2020 Category: Neurology Authors: Chen HC, Cao JX, Cai YT, Du HL, Xi XX, Sun J, Yin J, Gao LP, Jing YH Tags: Exp Neurol Source Type: research

Dcf1 deficiency induces hypomyelination by activating Wnt signaling.
Abstract Myelination is extremely important in achieving neural function. Hypomyelination causes a variety of neurological diseases. However, little is known about how hypomyelination occurs. Here we investigated the effect of dendritic cell factor 1(Dcf1) on myelination, using in vitro and in vivo models and found that Dcf1 is essential for normal myelination, motor coordination and balance. Lack of Dcf1 downregulated myelin-associated proteins, such as myelin basic protein (MBP), myelin associated glycoprotein (MAG), and 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in the hippocampus and corpus callosum ...
Source: Experimental Neurology - September 25, 2020 Category: Neurology Authors: Feng R, Wang J, Luo G, Wang H, Shi J, TieqiaoWen Tags: Exp Neurol Source Type: research

Subcutaneous anti-CD20 antibody treatment delays gray matter atrophy in human myelin oligodendrocyte glycoprotein-induced EAE mice.
Abstract BACKGROUND: The human myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (huMOG-EAE) model, generates B-cell driven demyelination in mice, making it a suitable multiple sclerosis model to study B cell depletion. OBJECTIVES: We investigated the effect of subcutaneous anti-CD20 antibody treatment on huMOG-EAE gray matter (GM) pathology. METHODS: C57Bl/6, 8-week old mice were immunized with 200 huMOG1-125 and treated with 50 μg/mouse of anti-CD20 antibody (n = 16) or isotype control (n = 16). Serial brain volumetric 9.4 T MRI scans was performed at ...
Source: Experimental Neurology - September 25, 2020 Category: Neurology Authors: Pol S, Liang S, Schweser F, Dhanraj R, Schubart A, Preda M, Sveinsson M, Ramasamy DP, Dwyer MG, Weckbecker G, Zivadinov R Tags: Exp Neurol Source Type: research

A micro-LED implant and technique for optogenetic stimulation of the rat spinal cord.
Abstract To date, relatively few studies have used optogenetic stimulation to address basic science and therapeutic questions within the spinal cord. Even less have reported optogenetic stimulation in the rat spinal cord. This is likely due to a lack of accessible optogenetic implants. The development of a device that can be fabricated and operated by most laboratories, requiring no special equipment, would allow investigators to begin dissecting the functions of specific neuronal cell-types and circuitry within the spinal cord, as well as investigate therapies for spinal ailments like spinal cord injury. Here, we...
Source: Experimental Neurology - September 25, 2020 Category: Neurology Authors: Mondello SE, Pedigo B, Sunshine, Fischedick AE, Horner PJ, Moritz CT Tags: Exp Neurol Source Type: research

Working memory training impacts neural activity during untrained cognitive tasks in people with multiple sclerosis.
Abstract The identification of effective cognitive rehabilitation strategies for people with multiple sclerosis (MS) is critically important, as cognitive difficulties are prevalent in MS. Relatively few cognitive rehabilitation studies in MS have examined working memory (WM) training specifically, and the extent that WM training may impact neural activity on untrained tasks is not well understood. In the present study, we examined the effects of 20 sessions of adaptive WM training (using an n-back task with visually presented letter stimuli) on neural indices of the transfer of training gains to untrained tasks i...
Source: Experimental Neurology - September 25, 2020 Category: Neurology Authors: Turtola ZP, Covey TJ Tags: Exp Neurol Source Type: research

Acute intermittent hypoxia boosts spinal plasticity in humans with tetraplegia.
We examined corticospinal function by measuring motor evoked potentials (MEPs) elicited by cortical and subcortical stimulation of corticospinal axons and voluntary motor output in the FDI muscle before and after 30 min of PCMS combined with AIH (PCMS+AIH) or sham AIH (PCMS+sham-AIH). The amplitude of MEPs evoked by magnetic and electrical stimulation increased after both protocols, but most after PCMS+AIH, consistent with the hypothesis that their combined effects arise from spinal plasticity. Both protocols increased electromyographic activity in the FDI muscle to a similar extent. Thus, PCMS effects on spinal synapses...
Source: Experimental Neurology - September 24, 2020 Category: Neurology Authors: Christiansen L, Chen B, Lei Y, Urbin MA, Richardson MSA, Oudega M, Sandhu M, Rymer WZ, Trumbower RD, Mitchell GS, Perez MA Tags: Exp Neurol Source Type: research

Stress and signaling pathways regulating autophagy: From behavioral models to psychiatric disorders.
Abstract Autophagy is a process of degradation and recycling of cytoplasmatic components by the lysosomes. In the central nervous system (CNS), autophagy is involved in cell surveillance, neuroinflammation, and neuroplasticity. Neuropsychiatric conditions are associated with functional disturbances at molecular and cellular levels, causing significant impairments in cell homeostasis. Additionally, emerging evidence supports that dysfunctions in autophagy contribute to the pathophysiology of neurological diseases. However, the studies on autophagy in psychiatric disorders are highly heterogeneous and have several l...
Source: Experimental Neurology - September 24, 2020 Category: Neurology Authors: Pierone BC, Pereira CA, Garcez ML, Kaster MP Tags: Exp Neurol Source Type: research

Wnt5b/Ryk-mediated membrane trafficking of P2X3 receptors contributes to bone cancer pain.
Abstract Wnt5b, a member of Wnt family, plays multiple roles in tumor progression and metastasis. However, whether Wnt5b contributes to the sensitization of dorsal root ganglia (DRG) neurons and pathogenesis of bone cancer pain still remains unclear. Here, we found that the protein expression of Wnt5b and its atypical tyrosine protein kinase receptor Ryk was upregulated in ipsilateral DRGs in tumor-bearing mice. Application of Wnt5b evoked an increased discharge frequency in isolated DRG neurons and pain hypersensitivity in naïve mice which were almost completely prevented by anti-Ryk antibody. Moreover, intr...
Source: Experimental Neurology - September 22, 2020 Category: Neurology Authors: He JJ, Wang X, Liang C, Yao X, Zhang ZS, Yang RH, Fang D Tags: Exp Neurol Source Type: research

Early phosphoproteomic changes in the retina following optic nerve crush.
This study provides new insights into mechanisms of RGC degeneration after ON injury, as well as central nervous system (CNS) neurodegeneration, since the retina is an extension of the CNS. These new insights will lead to novel therapeutic targets for retinal and CNS neurodegeneration. PMID: 32971066 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - September 20, 2020 Category: Neurology Authors: Liu Y, Zhong H, Bussan EL, Pang IH Tags: Exp Neurol Source Type: research

Facial grimace testing as an assay of neuropathic pain-related behavior in a mouse model of cervical spinal cord injury.
Abstract A major portion of individuals affected by traumatic spinal cord injury (SCI) experience one or more types of chronic neuropathic pain (NP), which is often intractable to currently available treatments. The availability of reliable behavioral assays in pre-clinical models of SCI-induced NP is therefore critical to assess the efficacy of new potential therapies. Commonly used assays to evaluate NP-related behavior in rodents, such as Hargreaves thermal and von Frey mechanical testing, rely on the withdrawal response to an evoked stimulus. However, other assays that test spontaneous/non-evoked NP-related be...
Source: Experimental Neurology - September 19, 2020 Category: Neurology Authors: Heinsinger NM, Spagnuolo G, Allahyari RV, Galer S, Fox T, Jaffe DA, Thomas SJ, Iacovitti L, Lepore AC Tags: Exp Neurol Source Type: research

Ampakines stimulate phrenic motor output after cervical spinal cord injury.
Abstract Activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors increases phrenic motor output. Ampakines are a class of drugs that are positive allosteric modulators of AMPA receptors. We hypothesized that 1) ampakines can stimulate phrenic activity after incomplete cervical spinal cord injury (SCI), and 2) pairing ampakines with brief hypoxia could enable sustained facilitation of phrenic bursting. Phrenic activity was recorded ipsilateral (IL) and contralateral (CL) to C2 spinal cord hemisection (C2Hx) in anesthetized adult rats. Two weeks after C2Hx, ampakine CX717 (15 mg/k...
Source: Experimental Neurology - September 15, 2020 Category: Neurology Authors: Wollman LB, Streeter KA, Fusco AF, Gonzalez-Rothi E, Sandhu MS, Greer JJ, Fuller DD Tags: Exp Neurol Source Type: research

Unique signatures of stress-induced senescent human astrocytes.
Abstract Senescence was recently linked to neurodegeneration and astrocytes are one of the major cell types to turn senescent under neurodegenerative conditions. Senescent astrocytes were detected in Parkinson's disease (PD) patients' brains besides reactive astrocytes, yet the difference between senescent and reactive astrocytes is unclear. We aimed to characterize senescent astrocytes in comparison to reactive astrocytes and investigate differences and similarities. In a cell culture model of human fetal astrocytes, we determined a unique senescent transcriptome distinct from reactive astrocytes which comprises ...
Source: Experimental Neurology - September 15, 2020 Category: Neurology Authors: Simmnacher K, Krach F, Schneider Y, Alecu JE, Mautner L, Klein P, Roybon L, Prots I, Xiang W, Winner B Tags: Exp Neurol Source Type: research

Nano-engineered nerolidol loaded lipid carrier delivery system attenuates cyclophosphamide neurotoxicity - Probable role of NLRP3 inflammasome and caspase-1.
Abstract Neuroinflammation is one of the most common etiology in various neurological disorders and responsible for multi-array neurotoxic manifestations such as neurodegeneration, neurotransmitters alteration and cognitive dysfunction. NR (Nerolidol) is a natural bioactive molecule which possesses significant antioxidant and anti-inflammatory potential, but suffers from glitches of low solubility, low bioavailability and fast hepatic metabolism. In the current study, we fabricated nano-engineered lipid carrier of nerolidol (NR-NLC) for its effective delivery into the brain and explored its effect on neuroinflamma...
Source: Experimental Neurology - September 13, 2020 Category: Neurology Authors: Iqubal A, Syed MA, Najmi AK, Azam F, Barreto GE, Iqubal MK, Ali J, Haque SE Tags: Exp Neurol Source Type: research

Serine residues 13 and 16 are key modulators of mutant huntingtin induced toxicity in Drosophila.
Abstract Poly-glutamine expansion near the N-terminus of the huntingtin protein (HTT) is the prime determinant of Huntington's disease (HD) pathology; however, post-translational modifications and protein context are also reported to influence poly-glutamine induced HD toxicity. The impact of phosphorylating serine 13/16 of mutant HTT (mHTT) on HD has been documented in cell culture and murine models. However, endogenous processing of the human protein in mammalian systems complicates the interpretations. Therefore, to study the impact of S13/16 phosphorylation on the subcellular behavior of HTT under a controlled...
Source: Experimental Neurology - September 13, 2020 Category: Neurology Authors: Chatterjee M, Steffan JS, Lukacsovich T, Marsh JL, Agrawal N Tags: Exp Neurol Source Type: research

The effect of type 2 diabetes on CD36 expression and the uptake of oxLDL: Diabetes affects CD36 and oxLDL uptake.
Abstract We investigated whether type 2 diabetes mellitus (T2DM), a risk factor of stroke, affects the level of scavenger receptor CD36 and the uptake of its ligand, oxidized LDL (oxLDL); and whether pioglitazone, a drug that enhances CD36, promotes oxLDL uptake. Compared to normoglycemic db/+ mice, adult db/db mice showed a pronounced reduction in surface CD36 expression on myeloid cells from the blood, brain, and bone marrow as detected by flow cytometry, which correlated with elevated plasma soluble-CD36 as determined by ELISA. Increased CD36 expression was found in brain macrophages and microglia of both genot...
Source: Experimental Neurology - September 10, 2020 Category: Neurology Authors: Kanoke A, Nishijima Y, Ljungberg M, Omodaka S, Yang SY, Wong S, Rabiller G, Tominaga T, Hsieh CL, Liu J Tags: Exp Neurol Source Type: research