Excitatory amino acid receptor subtype binding following traumatic brain injury

ArticleinBrain Research 526(1):103-7 · September 1990
DOI: 10.1016/0006-8993(90)90254-9 · Source: PubMed
Sprague-Dawley rats were subjected to a moderate level (2.2 atm) of traumatic brain injury (TBI) using fluid percussion. Injured animals were allowed post-trauma survival periods of 5 min, 3 and 24 h. Regional glutamate receptor subtype binding was assessed with quantitative autoradiography in each group for N-methyl-D-aspartate (NMDA), quisqualate and kainate receptor subpopulations at approximately the -3.8 bregma level and compared to a sham control group. [3H]glutamate binding to the NMDA receptor was significantly (P less than 0.05) decreased at 3 h post-TBI in the hippocampal CA1 stratum radiatum, the molecular layers of the dentate gyri and the outer (layers 1-3) and inner (layers 5 and 6) overlying neocortex. NMDA receptor binding was significantly reduced in layers 5 and 6 of the neocortex at all post-trauma survival times but no further differences were seen in the hippocampi. No significant changes were observed with [3H]AMPA binding to quisqualate receptors and [3H]KA binding was significantly reduced only in layers 5 and 6 of the neocortex at 24 h after TBI. These data further confirm the pathological involvement of the NMDA receptor complex in brain regions selectively vulnerable to moderate levels of TBI in this model.
    • "TBI alters hippocampal neurotransmitter systems involved in the generation of theta, including acetylcholine, glutamate and GABA (Saija et al., 1988; Faden et al., 1989; Katayama et al., 1990; Robinson et al., 1990; Marshall et al., 2002). Rapid and prolonged increases in neurotransmitter levels act on local receptors causing long-lasting adaptation (Miller et al., 1990; Delahunty, 1992; Jiang et al., 1994; Delahunty et al., 1995; Schwarzbach et al., 2006). Thus, even after the injury-induced alteration of extracellular concentration of neurotransmitters returns to basal levels, modified receptors may have an ectopic response to subsequent activation, potentially affecting the timing and strength of receptor coupled processes essential to rhythm generation (Lyeth et al., 1992; Fineman et al., 1993; Kato et al., 2007; Marcoux et al., 2008). "
    [Show abstract] [Hide abstract] ABSTRACT: Traumatic brain injury (TBI) can result in persistent cognitive, behavioral and emotional deficits. However, the vast majority of patients are not chronically hospitalized; rather they have to manage their disabilities once they are discharged to home. Promoting recovery to pre-injury level is important from a patient care as well as a societal perspective. Electrical neuromodulation is one approach that has shown promise in alleviating symptoms associated with neurological disorders such as in Parkinson's disease (PD) and epilepsy. Consistent with this perspective, both animal and clinical studies have revealed that TBI alters physiological oscillatory rhythms. More recently several studies demonstrated that low frequency stimulation improves cognitive outcome in models of TBI. Specifically, stimulation of the septohippocampal circuit in the theta frequency entrained oscillations and improved spatial learning following TBI. In order to evaluate the potential of electrical deep brain stimulation for clinical translation we review the basic neurophysiology of oscillations, their role in cognition and how they are changed post-TBI. Furthermore, we highlight several factors for future pre-clinical and clinical studies to consider, with the hope that it will promote a hypothesis driven approach to subsequent experimental designs and ultimately successful translation to improve outcome in patients with TBI.
    Article · Apr 2016
    • "While advances in an understanding of the functional alterations occurring in the CA1 and other brain regions improves patient care, no specific pharmacological therapy for TBI is currently available that would improve neurological, behavioral, and cognitive outcomes (Beauchamp et al., 2008 ). Indeed, treatments directed at AMPA receptors may be ineffective , as no significant differences in the binding of extracellular excitatory amino acids to AMPA receptors following brain injury have been observed (McIntosh, 1993; Miller et al., 1990 ). NMDA receptor antagonists may be effective within hours of a TBI to reduce overstimulation, but may be ineffective or counter-effective 7 days after TBI (Beauchamp et al., 2008). "
    [Show abstract] [Hide abstract] ABSTRACT: Patients that suffer mild traumatic brain injuries (mTBI) often develop cognitive impairments, including memory and learning deficits. The hippocampus shows a high susceptibility to mTBI-induced damage due to its anatomical localization and has been implicated in cognitive and neurological impairments after mTBI. However, it remains unknown whether mTBI cognitive impairments are a result of morphological and pathophysiological alterations occurring in the CA1 hippocampal region. We investigated whether mTBI induces morphological and pathophysiological alterations in the CA1 using the controlled cortical impact (CCI) model. Seven days after CCI, animals subjected to mTBI showed cognitive impairment in the passive avoidance test and deficits to long-term potentiation (LTP) of synaptic transmission. Deficiencies in inducing or maintaining LTP were likely due to an observed reduction in the activation of NMDA but not AMPA receptors. Significant reductions in the frequency and amplitude of spontaneous and miniature GABAA-receptor mediated inhibitory postsynaptic currents (IPSCs) were also observed 7days after CCI. Design-based stereology revealed that although the total number of neurons was unaltered, the number of GABAergic interneurons is significantly reduced in the CA1 region 7days after CCI. Additionally, the surface expression of α1, ß2/3, and γ2 subunits of the GABAA receptor were reduced, contributing to a reduced mIPSC frequency and amplitude, respectively. Together, these results suggest that mTBI causes a significant reduction in GABAergic inhibitory transmission and deficits to NMDA receptor mediated currents in the CA1, which may contribute to changes in hippocampal excitability and subsequent cognitive impairments after mTBI. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Jul 2015
    • "Secondary injury includes ischemia/ reperfusion injury, inflammation, oxidative stress, and glutamate excitotoxicity, all of which contribute to the eventual tissue degeneration and functional loss. A prevalent hypothesis is that TBI increases extracellular levels of the excitatory neurotransmitters such as glutamate (Choi, 1985Choi, , 1987Choi, , 1988 Braughler and Hall, 1989; Miller et al., 1990; Choi, 1992; Juurlink and Paterson, 1998; Hall and Springer, 2004; Yi and Hazell, 2006). Glutamate, in turn, causes excessive stimulation of N-methyl-D-aspartic acid receptors (NMDA), thus mediating calcium over influx and triggering rapid excitotoxic necrosis that results in traumatic damage to the central nervous system (CNS). "
    Full-text · Article · Jun 2014
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