Excitatory amino acid receptor subtype binding following traumatic brain injury.
ABSTRACT 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.
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ABSTRACT: Traumatic brain injury (TBI) can result in the development of posttraumatic epilepsy (PTE). Recently, we reported differential alterations in tonic and phasic GABA(A) receptor (GABA(A)R) currents in hippocampal dentate granule cells 90 days after controlled cortical impact (CCI) (Mtchedlishvili et al., 2010). In the present study, we investigated long-term changes in the protein expression of GABA(A)R α1, α4, γ2, and δ subunits, NMDA (NR2B) and AMPA (GluR1) receptor subunits, and heat shock proteins (HSP70 and HSP90) in the hippocampus of Sprague-Dawley rats evaluated by Western blotting in controls, CCI-injured animals without PTE (CCI group), and CCI-injured animals with PTE (PTE group). No differences were found among all three groups for α1 and α4 subunits. Significant reduction of γ2 protein was observed in the PTE group compared to control. CCI caused a 194% and 127% increase of δ protein in the CCI group compared to control (p<0.0001), and PTE (p<0.0001) groups, respectively. NR2B protein was increased in CCI and PTE groups compared to control (p=0.0001, and p=0.011, respectively). GluR1 protein was significantly decreased in CCI and PTE groups compared to control (p=0.003, and p=0.001, respectively), and in the PTE group compared to the CCI group (p=0.036). HSP70 was increased in CCI and PTE groups compared to control (p=0.014, and p=0.005, respectively); no changes were found in HSP90 expression. These results provide for the first time evidence of long-term alterations of GABA(A) and glutamate receptor subunits and a HSP following CCI.Epilepsy research 03/2011; 95(1-2):20-34. DOI:10.1016/j.eplepsyres.2011.02.008 · 2.19 Impact Factor
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ABSTRACT: Mild to moderate cases of traumatic brain injury (TBI) are very common, but are not always associated with the overt pathophysiogical changes seen following severe trauma. While neuronal death has been considered to be a major factor, the pervasive memory, cognitive and motor function deficits suffered by many mild TBI patients do not always correlate with cell loss. Therefore, we assert that functional impairment may result from alterations in surviving neurons. Current research has begun to explore CNS synaptic circuits after traumatic injury. Here we review significant findings made using in vivo and in vitro models of TBI that provide mechanistic insight into injury-induced alterations in synaptic electrophysiology. In the hippocampus, research now suggests that TBI regionally alters the delicate balance between excitatory and inhibitory neurotransmission in surviving neurons, disrupting the normal functioning of synaptic circuits. In another approach, a simplified model of neuronal stretch injury in vitro, has been used to directly explore how injury impacts the physiology and cell biology of neurons in the absence of alterations in blood flow, blood brain barrier integrity, or oxygenation associated with in vivo models of brain injury. This chapter discusses how these two models alter excitatory and inhibitory synaptic transmission at the receptor, cellular and circuit levels and how these alterations contribute to cognitive impairment and a reduction in seizure threshold associated with human concussive brain injury.Progress in brain research 02/2007; 161:143-69. DOI:10.1016/S0079-6123(06)61010-8 · 5.10 Impact Factor
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ABSTRACT: Traumatic brain injury (TBI) is predominantly a clinical problem of young persons, resulting in chronic cognitive and behavioral deficits. Specifically, the physiological response to a diffuse biomechanical injury in a maturing brain can clearly alter normal neuroplasticity. To properly evaluate and investigate developmental TBI requires an understanding of normal principles of cerebral maturation, as well as a consideration of experience-dependent changes. Changes in neuroplasticity may occur through many age-specific processes, and our understanding of these responses at a basic neuroscience level is only beginning. In this article, we will particularly discuss mechanisms of TBI-induced altered developmental plasticity such as altered neurotransmission, distinct molecular responses, cell death, perturbations in neuronal connectivity, experience-dependent 'good plasticity' enhancements and chronic 'bad plasticity' sequelae. From this summary, we can conclude that 'young is not always better' and that the developing brain manifests several crucial vulnerabilities to TBI.Developmental Neuroscience 02/2006; 28(4-5):364-79. DOI:10.1159/000094163 · 2.45 Impact Factor