Intracerebroventricularly Administered Neurotrophins Attenuate Blood–Cerebrospinal Fluid Barrier Breakdown and Brain Pathology following Whole-Body,Hyperthermia An Experimental Study in the Rat Using Biochemical and Morphological Approaches

摘要

Previous studies from our laboratory show that apart from blood–brain barrier (BBB) disruption, the blood–cerebrospinal fluid (CSF) barrier (BCSFB) for proteins is also broken down following wholebody hyperthermia (WBH) in a rat model. Breakdown of the BCSFB alters brain homeostasis and adversely affects the structure and function of the central nervous system (CNS). Since neurotrophins and growth factors (e.g., brain-derived growth factor [BDNF], glial cell line–derived neurotrophic factor [GONF], and insulin-like growth factor 1 [IGF-11) are known neuroprotective agents in traumatic and ischemic brain injuries, a possibility exists that these neurotrophins will also attenuate neuronal and choroidal injury in WBH. Subjection of adult rats to 4 h of WBH at 38°C in a biological oxygen demand (BOD) incubator exhibited a profound increase in BCSFB permeability to Evans blue and radioiodine. Degeneration of choroidal epithelial cells and underlying ependyma, dilatation of the lateral ventricular space, and degenerative changes in the adjacent neuropil were frequent. The hippocampus, caudate nucleus, thalamus, and hypothalamus showed profound BBB disruption and brain edema formation.