VEGF-C treatment enhances cerebrospinal fluid outflow during Toxoplasma gondii brain infection but does not improve cerebral edema

Am J Pathol. 2023 Dec 6:S0002-9440(23)00447-9. doi: 10.1016/j.ajpath.2023.11.008. Online ahead of print.ABSTRACTCerebral edema frequently develops in the setting of brain infection and can contribute to elevated intracranial pressure, a medical emergency. Currently, it is incompletely understood how excess fluid is cleared from the brain. Previous studies have shown that interstitial fluid is transported out of the brain along perivascular channels that collect into the cerebrospinal fluid (CSF)-filled subarachnoid space. CSF is then removed from the central nervous system through venous and lymphatic routes. Here, we test the hypothesis that increasing lymphatic drainage of CSF would promote clearance of cerebral edema fluid during infection with the neurotropic parasite Toxoplasma gondii. We first used fluorescent microscopy and MRI to show that C57BL/6 mice develop vasogenic edema four to five weeks after infection with T. gondii. We then evaluated how brain infection affects meningeal lymphatic function through tracer experiments and demonstrated a decreased rate in CSF outflow in T. gondii-infected mice. Next, we treated mice with a VEGF-C-expressing viral vector, which induced meningeal lymphangiogenesis and improved CSF outflow in chronically infected mice. Finally, we compared brain water content in mice that received VEGF-C or sham treatment and observed no difference in cerebral edema. Therefore, while VEGF-C treatment can improve lymphatic outflow in mice infected ...
Source: Am J Pathol - Category: Pathology Authors: Source Type: research