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Neuritin improves the neurological functional recovery after experimental intracerebral hemorrhage in mice
In this study, ICH was induced in C57BL/6 J mice by injection of collagenase VII, while the overexpression of Nrn in the striatum was induced by an adeno-associated virus serotype 9 (AAV9) vector. We found that compared with GFP-ICH mice, Nrn-ICH mice showed improved performance in the corner, cylinder and forelimb tests after ICH, and showed less weight loss and more rapid weight recovery. Overexpression of Nrn reduced brain lesions, edema, neuronal death and white matter and synaptic integrity dysfunction caused by ICH. Western blot results showed that phosphorylated PERK and ATF4 were significantly inhibited, while phos...
Source: Neurobiology of Disease - May 31, 2021 Category: Neurology Authors: Junmei Lu Zhaoyang Li Qianru Zhao Dongdong Liu Yan-Ai Mei Source Type: research

Issue Cover (March 2021)
Front cover:Necrostatin ‐1 (Nec‐1) has been shown to inhibit necroptosis. The mitochondrial protein Bcl‐2/adenovirus E1B 19‐kDa interacting protein 3 (BNIP3) activates a type of caspase‐independent cell death that is similar to necroptosis. Here we show that Nec‐1 is protective against death of neurons and olig odendrocytes in traumatic brain injury (TBI) in mice and in ischemic stroke in rats by inhibiting BNIP3; Nec‐1 prevents BNIP3 from integration into mitochondria to block the BNIP3 cell death pathway. The data suggest that Nec‐1 is a novel inhibitor for BNIP3.Image Content: Nec‐1 preserves structur...
Source: Journal of Neurochemistry - April 2, 2021 Category: Neuroscience Tags: Issue Cover Source Type: research

Treatment with AAV1-Rheb(S16H) provides neuroprotection in a mouse model of photothrombosis-induced ischemic stroke
We recently reported that upregulation of the constitutively active ras homolog enriched in brain [Rheb(S16H)], which induces the activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, can protect adult neurons, mediated by the induction of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), in animal models of neurodegenerative diseases. Here we show that neuronal transduction of Rheb(S16H) using adeno-associated virus serotype 1 provides neuroprotection in a mouse model of photothrombosis-induced ischemic stroke. Rheb(S16H)-expressing neurons exhibited neurotrophic effec...
Source: NeuroReport - August 13, 2020 Category: Neurology Tags: Degeneration and Repair Source Type: research

ClC-3 induction protects against cerebral ischemia/reperfusion injury through promoting Beclin1/Vps34-mediated autophagy
AbstractAcute ischemic stroke is a devastating disease with very limited therapeutics. Growing appreciation of dysregulated autophagy contributes to the progression of brain ischemic injury, making it to be an appealing intervention target. In terms of its well-characterized consequences, the signal molecules required for autophagy activation are rather poorly defined. Here, we found the induction of chloride channel-3 (ClC-3) directly activated autophagy, which played an important role in limiting cerebral ischemia/reperfusion (I/R) injury. Further mechanism exploration discovered that the up-regulation of ClC-3 was criti...
Source: Human Cell - August 8, 2020 Category: Cytology Source Type: research

Presynaptic Caytaxin prevents apoptosis via deactivating DAPK1 in the acute phase of cerebral ischemic stroke.
Abstract Death-associated protein kinase 1 (DAPK1) is a key protein that mediates neuronal death in ischemic stroke. Although the substrates of DAPK1 and molecular signal in stroke have been gradually discovered, the modulation of DAPK1 itself is still unclear. Here we first reveal that Caytaxin, a brain-specific member of BCL2/adenovirus E1B -interacting protein (BNIP-2), increases and interacts with DAPK1 as early as 2 h after middle cerebral artery occlusion (MCAO) in the penumbra area of mouse brain. Furthermore, Caytaxin binds to DAPK1 at the presynaptic site and inhibits DAPK1 catalytic activity. Silencing...
Source: Experimental Neurology - April 7, 2020 Category: Neurology Authors: Wang S, Chen K, Yu J, Wang X, Li Q, Lv F, Shen H, Pei L Tags: Exp Neurol Source Type: research

Knockdown of Arginyl-tRNA Synthetase Attenuates Ischemia-Induced Cerebral Cortex Injury in Rats After Middle Cerebral Artery Occlusion
AbstractSome researchers have previously shown that RNAi knockdown of arginyl-tRNA synthetase (ArgRS) before or after a hypoxic injury can rescue animals from death, based on the model organism,C. elegans. However, there has been no study on the application of arginyl-tRNA synthetase knockdown in treating mammalian ischemic stroke, and its potential mechanism and effect on ischemic brain damage are still unknown. Here, we focused on the Rars gene, which encodes an arginyl-tRNA synthetase, and examined the effects of Rars knockdown in a permanent middle cerebral artery occlusion model in rats. To achieve this aim, adult mal...
Source: Translational Stroke Research - March 26, 2020 Category: Neurology Source Type: research

Molecular profile of the rat peri-infarct region four days after stroke: Study with MANF.
In this study, we examine the molecular profile of the peri-infarct region on post-stroke day four, time when reparative processes are ongoing. We used a multiomics approach, involving RNA sequencing, and mass spectrometry-based proteomics and metabolomics to characterize molecular changes in the peri-infarct region. We also took advantage of our previously developed method to express transgenes in the peri-infarct region where self-complementary adeno-associated virus (AAV) vectors were injected into the brain parenchyma on post-stroke day 2. We have previously used this method to show that mesencephalic astrocyte-derived...
Source: Experimental Neurology - March 26, 2020 Category: Neurology Authors: Teppo J, Vaikkinen A, Stratoulias V, Mätlik K, Anttila JE, Smolander OP, Pöhö P, Harvey BK, Kostiainen R, Airavaara M Tags: Exp Neurol Source Type: research

HIF ‑1α attenuates neuronal apoptosis by upregulating EPO expression following cerebral ischemia‑reperfusion injury in a rat MCAO model.
HIF‑1α attenuates neuronal apoptosis by upregulating EPO expression following cerebral ischemia‑reperfusion injury in a rat MCAO model. Int J Mol Med. 2020 Jan 28;: Authors: Li J, Tao T, Xu J, Liu Z, Zou Z, Jin M Abstract Hypoxia‑inducible factor‑1α (HIF‑1α) is a key transcriptional factor in response to hypoxia and is involved in ischemic stroke. In the present study, the potential for HIF‑1α to inhibit neuronal apoptosis through upregulating erythropoietin (EPO) was investigated in a transient middle cerebral artery occlusion (tMCAO) rat stroke model. For this purpose, a recombinant ...
Source: International Journal of Molecular Medicine - January 27, 2020 Category: Molecular Biology Authors: Li J, Tao T, Xu J, Liu Z, Zou Z, Jin M Tags: Int J Mol Med Source Type: research

An update on clinical, pathological, diagnostic, and therapeutic perspectives of childhood leukodystrophies.
Authors: Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR Abstract Introduction: Leukodystrophies constitute heterogenous group of rare heritable disorders primarily affecting the white matter of central nervous system. These conditions are often under-appreciated among physicians. The first clinical manifestations of leukodystrophies are often nonspecific and can occur in different ages from neonatal to late adulthood periods. The diagnosis is, therefore, challenging in most cases.Area covered: Herein, the authors discuss different aspects of leukodystrophies. The authors used...
Source: Expert Review of Neurotherapeutics - December 13, 2019 Category: Neurology Tags: Expert Rev Neurother Source Type: research

MST4 modulates the neuro-inflammatory response by regulating I κBα signaling pathway and affects the early outcome of experimental ischemic stroke in mice.
MST4 modulates the neuro-inflammatory response by regulating IκBα signaling pathway and affects the early outcome of experimental ischemic stroke in mice. Brain Res Bull. 2019 Nov 10;: Authors: Luan D, Zhang Y, Yuan L, Chu Z, Ma L, Xu Y, Zhao S Abstract MST4 limits peripheral, macrophage-dependent inflammatory responses through direct phosphorylation of the adaptor TRAF6; though its role in neuro-inflammation is unclear. We investigated microglia expression of MST4 and whether is attenuates neuro-inflammatory response after cerebral ischemia-reperfusion injury in mice. Adult male C57BL6 mice were su...
Source: Brain Research Bulletin - November 9, 2019 Category: Neurology Authors: Luan D, Zhang Y, Yuan L, Chu Z, Ma L, Xu Y, Zhao S Tags: Brain Res Bull Source Type: research

Reduction of glyoxalase 1 (GLO1) aggravates cerebrovascular remodeling via promoting the proliferation of basilar smooth muscle cells in hypertension.
Abstract Uncontrollable vascular smooth cell proliferation is responsible for vascular remodeling during hypertension development. Glyoxalase 1 (GLO1), the major enzyme detoxifying methylglyoxal, has a critical role in regulating proliferation of several cell types. However, little is known whether GLO1 is involved in cerebrovascular remodeling and basilar smooth muscle cell (BASMC) proliferation during hypertension. Here we explored the role of GLO1 in angiotensin II (Ang II)-induced cerebrovascular remodeling and proliferation of BASMCs and the underlying mechanisms. The protein expression of GLO1 in basilar art...
Source: Biochemical and Biophysical Research communications - August 12, 2019 Category: Biochemistry Authors: Gao M, Sun L, Liu YL, Xie JW, Qin L, Xue J, Wang YT, Guo KM, Ma MM, Li XY Tags: Biochem Biophys Res Commun Source Type: research

Effects of GDNF-Transfected Marrow Stromal Cells on Rats with Intracerebral Hemorrhage
Objective: The present study aimed to investigate the effects of Mesenchymal stem cells/glial cell line derived neurotrophic factor (MSCs/GDNF) transplantation on nerve reconstruction in rats with intracerebral hemorrhage. Methods: GDNF transduction to MSCs was using adenovirus vector pAdEasy-1-pAdTrack-CMV prepared. Intracerebral hemorrhage (ICH) was induced by injection of collagenase and heparin into the caudate putamen. At the third day after a collagenase-induced ICH, adult male SD rats were randomly divided into saline group, MSCs group and MSCs/GDNF group.
Source: Journal of Stroke and Cerebrovascular Diseases - June 23, 2019 Category: Neurology Authors: Li Deng, Xiaoqing Gao, Guangbi Fan, Chaoxian Yang Source Type: research

LRG1 Promotes Apoptosis and Autophagy through the TGFβ-smad1/5 Signaling Pathway to Exacerbate Ischemia/Reperfusion Injury
In this study, we discussed the function and mechanism of LRG1 in acute ischemic stroke from both basic and clinical research points of view. Mice underwent transient middle cerebral artery occlusion (tMCAO) surgery two weeks after LRG1 was overexpressed by the delivery of adeno-associated virus (AAV). For wild-type mice, both the protein and the transcript of LRG1 in the brain tissue were elevated after tMCAO. Meanwhile, the serum levels of LRG1 were decreased after tMCAO. The neuronal injury was shown aggravated in the AAV-LRG1 group (AAV-LRG1 mice with tMCAO) through infarction volume, neurological score, HE, and Nissl ...
Source: Neuroscience - June 18, 2019 Category: Neuroscience Source Type: research

Therapeutic potential of AAV9-S15D-RLC gene delivery in humanized MYL2 mouse model of HCM
This study is focused on aspartic acid-to-valine (D166V) mutation in the myosin regulatory light chain, RLC (MYL2 gene), associated with a malignant form of HCM. Since myosin RLC phosphorylation is critical for normal cardiac function, we aimed to exploit this post-translational modification via phosphomimetic-RLC gene therapy. We hypothesized that mimicking/modulating cardiac RLC phosphorylation in non-phosphorylatable D166V myocardium would improve heart function of HCM-D166V mice. Adeno-associated virus, serotype-9 (AAV9) was used to deliver phosphomimetic human RLC variant with serine-to-aspartic acid substitution at S...
Source: Journal of Molecular Medicine - May 16, 2019 Category: Molecular Biology Source Type: research

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