A New Model for Diffuse Brain Injury by Rotational Acceleration: II. Effects on Extracellular Glutamate, Intracranial Pressure, and Neuronal Apoptosis

Abstract

The aim of this study is to monitor excitatory amino acids (EAAs) in the extracellular fluids of the brain and to characterize regional neuronal damage in a new experimental model for brain injury, in which rabbits were exposed to 180-260 krad/s2 rotational head acceleration. This loading causes extensive subarachnoid hemorrhage, focal tissue bleeding, reactive astrocytosis, and axonal damage. Animals were monitored for intracranial pressure (ICP) and for amino acids in the extracellular fluids. Immunohistochemistry was used to study expression of the gene c-Jun and apoptosis with the terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) technique. Extracellular glutamate, glycine, and taurine increased significantly in the hippocampus within a few hours and remained high after 24 h. Neuronal nuclei in the granule layers of the hippocampus and cerebellum were positive for c-Jun after 24 h. Little immunoreactivity was detected in the cerebral cortex. c-Jun-positive neuronal perikarya and processes were found in granule and pyramidal CA4 layers of the hippocampus and among the Purkinje cells of the cerebellum. Also some microglial cells stained positively for c-Jun. TUNEL reactivity was most intense at 10 days after trauma and was extensive in neurons of the cerebral cortex, hippocampus, and cerebellum. The initial response of the brain after rotational head injury involves brain edema after 24 h and an excitotoxic neuronal microenvironment in the first hour, which leads to extensive delayed neuronal cell death by apoptosis necrosis in the cerebral cortex, hippocampus and cerebellum.

Pharmacotherapy to Improve the Acquired Aphasia following Brain Damages: A Review Study

“…The evidence support the effective role of glutamate stimulus neurotransmitter as a biological mechanism responsible for secondary neuronal process after brain lesion (83,84). Apoptotic process in neurons and neuroglial usually associated with cerebral edema have been shown in both focal and diffuse neurodegenerative damage (85,86). These pathological consequences are strongly related to cognitive, behavioral and emotional deficits after brain damage at all severity levels of injuries (87).…”

Identification and Characterization of Heterogeneous Neuronal Injury and Death in Regions of Diffuse Brain Injury: Evidence for Multiple Independent Injury Phenotypes

“…Evidence for diffuse involvement of the neuraxis in terms of injured neuronal somata has been limited in humans and animals (Lin et al, 2001;Runnerstam et al, 2001;Cernak et al, 2002). Although it is recognized that DBI evokes diffuse axonal damage, the neuronal somatic consequences of this event are not well understood.…”

“…This limited understanding of potential neuronal cell perturbation and loss occurring after DBI stands in contrast to the well documented cell death that occurs with focal injury . Isolated descriptions of scattered necrotic and apoptotic cell loss occurring after diffuse insults can be found in the literature, yet the mechanisms involved in the pathogenesis of these diffuse changes have not been characterized (Smith et al, 1997;Finnie et al, 2000;Lin et al, 2001;Runnerstam et al, 2001;Cernak et al, 2002).…”

Plasma taurine as a predictor of poor outcome in patients with mild neurological deficits after aneurysmal subarachnoid hemorrhage

“…4,7,11 Because of DCV and other complications, the mortality associated with SAH remains at 30%-50% as a result of early and delayed ischemic processes and the elevation of intracranial pressure along with diminished cerebral perfusion. 16 However, other mechanisms may influence a patient's outcome given that only 54% of those with DCV and 16% of those without it have a poor outcome. 22 Brain edema also occurs in SAH and may influence patient outcome, although it may not be detected by routine imaging methods.…”