Concurrent loss and proliferation of astrocytes following lateral fluid percussion brain injury in the adult rat

Abstract

Astrocyte populations were analyzed over a period of 1 month in the hippocampus following lateral fluid percussion (FP) brain injury. Rats (n = 23) were subjected either to a brain injury of moderate severity, or to anesthesia and surgery without injury (n = 7). At 3 days, 1, 2, or 4 weeks postinjury, subgroups of animals were sacrificed and the brains removed and sectioned for histochemical analysis. The density of astrocytes, identified with gold sublimate staining, decreased significantly in the ipsilateral hippocampus of injured rats 3 days following injury, eventually falling to 64% of the total astrocyte population present in uninjured animals by 1 week postinjury. One month postinjury, the density of hippocampal astrocytes had returned to 85% of the total number of astrocytes observed in the hippocampus of uninjured animals. In order to characterize the post-traumatic formation of new astrocytes, immunohistochemistry was performed using antibodies to proliferating cell nuclear antigen (PCNA) and to glial fibriallary acidic protein (GFAP). Positive immunolabeling for both PCNA and GFAP was most abundant at 3 days following FP brain injury in regions where the blood brain barrier was compromised, and was not detectable by 1 month postinjury. These results indicate that astrocyte proliferation after injury may be evoked by mitogens released from vascular sources, and may be an attempt to compensate for some of the astrocytic cell loss observed after injury.

Chronic cerebrovascular dysfunction after traumatic brain injury

“…Finally, astrocytes, which are a key component of the BBB (Abbott et al, ), have been shown to be decreased in number after LFP injury in the adult rat hippocampus (Hill‐Felberg et al, ; Zhao et al, ), contributing to BBB alteration. Astrocyte loss starts as early as 30 min postinjury and continues until 24 hr (Zhao et al, ).…”

“…Another study focused on later time points and showed that the astrocyte population in the injured hippocampus at 7 days was reduced by 64% of the total population compared with uninjured rats. After 1 month, the astrocyte population is restored to 85%, showing compensation for the earlier cell loss (Hill‐Felberg et al, ).…”

Lateral Fluid Percussion Brain Injury: A 15-Year Review and Evaluation

“…Acute damage progresses to apoptotic and necrotic neuronal death after LFP in rodents and remains detectable for months (Dietrich et al, 1994b;Rink et al, 1995;Hicks et al, 1996;Yakovlev et al, 1997;Bramlett et al, 1997b;Conti et al, 1998;Keane et al, 2001;Bramlett et al, 2002;Raghupathi et al, 2002;Knoblach et al, 2002b). Moreover, glial susceptibility to the pathology associated with LFP has been demonstrated at both acute and chronic time points throughout the brain (Cortez et al, 1989;Hill et al, 1996;Conti et al, 1998;Carbonell et al, 1999;D'Ambrosio et al, 1999;Hill-Felberg et al, 1999;Zhao et al, 2003;Grady et al, 2003). Regional degeneration can be identified by astrocyte, macrophage and microglia activation (Lowenstein et al, 1992;Soares et al, 1995a;Okimura et al, 1996;Bramlett et al, 1997a;Hill-Felberg et al, 1999;Zhao et al, 2003;Grady et al, 2003).…”

“…Moreover, glial susceptibility to the pathology associated with LFP has been demonstrated at both acute and chronic time points throughout the brain (Cortez et al, 1989;Hill et al, 1996;Conti et al, 1998;Carbonell et al, 1999;D'Ambrosio et al, 1999;Hill-Felberg et al, 1999;Zhao et al, 2003;Grady et al, 2003). Regional degeneration can be identified by astrocyte, macrophage and microglia activation (Lowenstein et al, 1992;Soares et al, 1995a;Okimura et al, 1996;Bramlett et al, 1997a;Hill-Felberg et al, 1999;Zhao et al, 2003;Grady et al, 2003). The initial increase in neutrophils lining the vasculature spreads into surrounding contused tissue (Soares et al, 1995a), while damage and loss of endothelial cells demonstrate significant alterations to the microvascula-LATERAL FLUID PERCUSSION BRAIN INJURY ture (Balabanov et al, 2001;Lin et al, 2001).…”

Plasticity following Injury to the Adult Central Nervous System: Is Recapitulation of a Developmental State Worth Promoting?

“…Similarly, unilateral excitotoxic or mechanical lesion of the DG results in a significant increase in proliferating cells on the lesioned side, most of which were located in the granule cell layer and expressed markers of mature granule neurons by 3 weeks after the lesion . After TBI, proliferation of astrocytes and activated microglia within the site of injury and hippocampus has been reported (Giordana et al, 1994;Hill-Felberg et al, 1999;Tzeng and Wu, 1999). Whether these new glial cells derive from the neurogenic regions or from parenchymal precursors remains to be elucidated.…”