Bedolla, A. | Search bioRxiv

bioRxiv2024

The choroid plexus maintains ventricle volume and adult subventricular zone neuroblast pool, which facilitates post-stroke neurogenesis

The brains neuroreparative capacity after injuries such as ischemic stroke is contained in the brains neurogenic niches, primarily the subventricular zone (SVZ), which lies in close contact with the cerebrospinal fluid (CSF) produced by the choroid plexus (ChP). Despite the wide range of their proposed functions, the ChP/CSF remain among the most understudied compartments of the central nervous system (CNS). Here we report a mouse genetic tool (the ROSA26iDTR mouse line) for non-invasive, specific, and temporally controllable ablation of CSF-producing ChP epithelial cells to assess the roles of the ChP and CSF in brain homeostasis and injury. Using this model, we demonstrate that ChP ablation causes rapid and permanent CSF volume loss accompanied by disruption of ependymal cilia bundles. Surprisingly, ChP ablation did not result in overt neurological deficits at one-month post-ablation. However, we observed a pronounced decrease in the pool of SVZ neuroblasts following ChP ablation, which occurs due to their enhanced migration into the olfactory bulb. In the MCAo model of ischemic stroke, neuroblast migration into the lesion site was also reduced in the CSF-depleted mice. Thus, our study establishes an important and novel role of ChP/CSF in regulating the regenerative capacity of the adult brain under normal conditions and after ischemic stroke.

neuroscience↗

bioRxiv2020

Indirect traumatic optic neuropathy after head trauma in adolescent male mice is associated with behavioral visual impairment, neurodegeneration, and elevated endoplasmic reticulum stress markers at acute and subacute times.

Traumatic brain injury (TBI) results in a number of impairments, often including visual symptoms. In some cases, visual symptoms after head trauma are mediated by traumatic injury to the optic nerve, termed traumatic optic neuropathy (TON), which has few effective options for treatment. Using a murine closed-head weight-drop model of head trauma, we have previously reported in adult mice that there is relatively selective injury to the optic tract and thalamic/brainstem projections of the visual system. In the current study, we performed blunt head trauma on adolescent C57BL/6 mice, and investigated visual impairment in the primary visual system, now including the retina, using behavioral and histologic methods at multiple time points. After injury, mice displayed evidence of decreased optomotor responses illustrated by decreased optokinetic nystagmus. There did not appear to be a significant change in circadian locomotor behavior patterns, although there was an overall decrease in locomotor behavior in mice with head injury. There was evidence of axonal degeneration of optic nerve fibers with associated retinal ganglion cell death. There was also evidence of astrogliosis and microgliosis in major central targets of optic nerve projections. Further, there was elevated expression of endoplasmic reticulum (ER) stress markers in retinas of injured mice. Visual impairment, histologic markers of gliosis and neurodegeneration, and elevated ER stress marker expression persisted for at least 30 days after injury. The current results extend our previous findings in adult mice into adolescent mice, provide direct evidence of retinal ganglion cell injury after head trauma, and suggest that axonal degeneration is associated with elevated ER stress in this model of TON.

neuroscience↗