Experimental epidural hematoma causes cerebral infarction and activates neocortical glial and neuronal genesis in adult guinea pigs

Abstract

Epidural hematoma (EDH) is a type of life-threatening traumatic brain injury. Little is known about the extent to which EDH may cause neural damage and regenerative response in the cerebral cortex. Here we attempted to explore these issues by using guinea pigs as an experimental model. Unilateral EDH was induced by injection of 0.1 ml autologous blood into the extradural space, with experimental effects examined at 7, 14, 30, and 60 days postlesion. An infarct developed in the cortex deep to the EDH largely after 7 days postlesion, with neuronal death occurred from layers I to V in the central infarct region, as evidenced by loss of immunoreactivity (IR) for neuron-specific nuclear antigen (NeuN). Glial fibrillary acidic protein (GFAP) IR appeared as a cellular band surrounding the infarct and extending into the periinfarct cortex along the pia. Doublecortin (DCX) IR emerged in these same areas, with labeled cells appearing as astrocytic and neuronal profiles. DCX/GFAP colocalization was found in these regions commonly at 7 and 14 days postlesion, whereas DCX/NeuN-colabeled neurons were detectable at 30 and 60 days postlesion. Subpopulations of GFAP-, DCX-, or NeuN-immunoreactive cells colocalized with the endogenous proliferative marker Ki-67 or bromodeoxyuridine (BrdU) after pulse-chase with this birth-dating marker. The results suggest that experimental EDH can cause severe neuronal loss, induce significant glial activation, and promote a certain degree of local neuronal genesis in adult guinea pig neocortex. These findings point to potential therapeutic targets for improving neuronal recovery in clinical management of EDH.

Assessment of the role of intracranial hypertension and stress on hippocampal cell apoptosis and hypothalamic-pituitary dysfunction after TBI

“…A standardized epidural hematoma model was based on previous reports 13, 18, 25 . Briefly, before surgery, general anesthesia was performed with 0.3 ml/100 g chloral hydrate administered intraperitoneally.…”

“…Experimental studies have been performed with epidural balloon inflation, epidural hematoma, or ischemia models to study the physiological, histopathological and biochemical changes in the brain parenchyma that are caused by brain displacement or intracranial hypertension 15–18 . Although many clinical trials have focused on dysfunction of the hypothalamic-pituitary axis caused by TBI 10, 19–21 , few studies have paid close attention to neuroendocrine and physiopathological alterations of the hypothalamic-pituitary axis induced by TBI in the acute phase.…”

Proliferation and Glia-Directed Differentiation of Neural Stem Cells in the Subventricular Zone of the Lateral Ventricle and the Migratory Pathway to the Lesions after Cortical Devascularization of Adult Rats

“…Cerebral ischemic stroke is a leading cause of human death and disability [ 1 – 3 ]. Stroke and traumatic brain injury lead to cell death, characterized by a loss of neurons and glial cells within the brain [ 4 , 5 ]. In the early 1990s, self-replicating neural stem cells (NSCs) were identified in the central nervous system (CNS).…”