Acute neuropathological sequelae and neural tissue transplantation in experimental traumatic brain injury

Date of Completion

January 1993

Keywords

Biology, Neuroscience

Degree

Ph.D.

Abstract

Unfortunately, very little is known about selective neuronal degeneration and acute inflammatory processes following human non-missile head injuries. The present thesis employs lateral fluid percussion (LFP) in the rat to examine traumatic neuronal degeneration, blood brain barrier (BBB) breakdown, and acute inflammation after experimental contusive brain injury. In addition, the present thesis also characterizes the efficacy of fetal neural tissue transplantation as a therapeutic alternative to pharmacology following traumatic brain injury (TBI).^ LFP in the rat produced a focal contusion within ipsilateral cortex and thalamus. Diffuse neuronal degeneration occurred bilaterally within hippocampus, substantia nigra, superior colliculus, and posterior pons. BBB breakdown, as evidenced by IgG and C3 extravasation, was maximal throughout injured cortex and hippocampus with small focal regions observed in diffuse subcortical structures. Interestingly, neuronal degeneration within subcortical structures often took place in the absence of BBB breakdown. The preceding observation suggests that selective neuronal degeneration may occur following TBI. Neuronal and glial cells as well as plaque-like formations within injured regions were also immunopositive for IgG and C3. Neutrophils were observed within contused cortex and hippocampus during the acute post injury period. Activated macrophages predominated within contused cortex at seventy two hours post trauma. Almost no neutrophils or activated macrophages appeared within injured diencephalic or midbrain areas except in regions exhibiting focal hemorrhage. In conclusion, selective subcortical neuronal degeneration can occur following contusive trauma. Acute inflammatory events were confined to injured cortex. The difference in neuropathological sequelae between cortical and subcortical structures raises the possibility that different mechanisms may be involved following TBI.^ E16 fetal cortical tissue, grafted into injured cortex within two weeks post injury, survived and attenuated glial scarring. However, grafts transplanted four weeks after injury fared poorly and had no effect upon glial scar formation. In addition, fetal cortical transplants did not improve neurological motor deficits associated with LFP brain injury. Nevertheless, E16 fetal hippocampal tissue transplanted into contused cortex, successfully ameliorated hippocampal CA3 neuronal loss resulting from LFP. In conclusion, fetal neural tissue transplantation, when applied under specific guidelines, can attenuate glial scarring and spare hippocampal CA3 neural loss following TBI. ^

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