Novel therapeutic modulators of astrocytes for hydrocephalus

Abstract

Hydrocephalus is mainly characterized by excessive production or impaired absorption of cerebrospinal fluid that causes ventricular dilation and intracranial hypertension. Astrocytes are the key response cells to inflammation in the central nervous system. In hydrocephalus, astrocytes are activated and show dual characteristics depending on the period of development of the disease. They can suppress the disease in the early stage and may aggravate it in the late stage. More evidence suggests that therapeutics targeting astrocytes may be promising for hydrocephalus. In this review, based on previous studies, we summarize different forms of hydrocephalus-induced astrocyte reactivity and the corresponding function of these responses in hydrocephalus. We also discuss the therapeutic effects of astrocyte regulation on hydrocephalus in experimental studies.

Cerebral furin deficiency causes hydrocephalus in mice

“…The role of astrocytes in hydrocephalus is not conclusive. 72 It is reported that in an animal model of hyh mice, astrocytes form a layer at the denuded ventricular lining, 44 supporting that astroglial reaction may compensate for the loss of homeostasis. 73 However, in a mouse model of Bardet–Biedl syndrome (BBS) caused by BBS8 deletion, the enhanced GFAP protein correlates with the development of hydrocephalus, 74 suggesting that astrocytes play a role in causing this phenotype.…”

Microcirculatory Impairment and Cerebral Injury in Hydrocephalus and the Effects of Cerebrospinal Fluid Diversion

“…Reactive astrogliosis was observed throughout the cerebral mantle. 14 These changes, particularly pronounced in advanced hydrocephalus, indicated the significant impact of hydrocephalus on CBF and associated brain alterations. 2,38 This study did not find a significant increase in ICP in the hydrocephalic group compared with the control group, and there was no significant correlation between ICP and CBF.…”

“…Reactive astrogliosis was observed throughout the cerebral mantle. 14 These changes, particularly pronounced in advanced hydrocephalus, indicated the significant impact of hydrocephalus on CBF and associated brain alterations. 2,38…”

“…12,13 In response to cerebral injury, astrocytes become reactive, undergo hypertrophy, increase in number, and upregulate the expression of glial fibrillary acidic protein (GFAP). 14,15 In severe hydrocephalus, the cortical layers are damaged. This leads to neuronal degeneration, which includes pyknosis, cellular shrinkage, and eventually cell loss.…”