The Experts below are selected from a list of 30 Experts worldwide ranked by ideXlab platform
Helen M Bramlett - One of the best experts on this subject based on the ideXlab platform.
-
post traumatic Seizure susceptibility is attenuated by hypothermia therapy
European Journal of Neuroscience, 2010Co-Authors: Coleen M Atkins, Jessie S Truettner, George Lotocki, Juliana Sanchezmolano, Yuan Kang, Ofelia F Alonso, Thomas J Sick, Dalton W Dietrich, Helen M BramlettAbstract:Traumatic brain injury (TBI) is a major risk factor for the subsequent development of epilepsy. Currently, chronic Seizures after brain injury are often poorly controlled by available antiepileptic drugs. Hypothermia treatment, a modest reduction in brain temperature, reduces inflammation, activates pro-survival signaling pathways, and improves cognitive outcome after TBI. Given the well-known effect of therapeutic hypothermia to ameliorate pathological changes in the brain after TBI, we hypothesized that hypothermia therapy may attenuate the development of Post-Traumatic epilepsy and some of the pathomechanisms that underlie Seizure formation. To test this hypothesis, adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury, and were then maintained at normothermic or moderate hypothermic temperatures for 4 h. At 12 weeks after recovery, Seizure susceptibility was assessed by challenging the animals with pentylenetetrazole, a GABA(A) receptor antagonist. Pentylenetetrazole elicited a significant increase in Seizure frequency in TBI normothermic animals as compared with sham surgery animals and this was significantly reduced in TBI hypothermic animals. Early hypothermia treatment did not rescue chronic dentate hilar neuronal loss nor did it improve loss of doublecortin-labeled cells in the dentate gyrus post-Seizures. However, mossy fiber sprouting was significantly attenuated by hypothermia therapy. These findings demonstrate that reductions in Seizure susceptibility after TBI are improved with Post-Traumatic hypothermia and provide a new therapeutic avenue for the treatment of Post-Traumatic epilepsy.
Jason H Huang - One of the best experts on this subject based on the ideXlab platform.
-
nkcc1 up regulation contributes to early post traumatic Seizures and increased post traumatic Seizure susceptibility
Brain Structure & Function, 2017Co-Authors: Fushun Wang, Xiaowei Wang, Lee A Shapiro, Maria L Cotrina, Weimin Liu, Ernest W Wang, Wei Wang, Jason H HuangAbstract:Traumatic brain injury (TBI) is not only a leading cause for morbidity and mortality in young adults (Bruns and Hauser, Epilepsia 44(Suppl 10):210, 2003), but also a leading cause of Seizures. Understanding the Seizure-inducing mechanisms of TBI is of the utmost importance, because these Seizures are often resistant to traditional first- and second-line anti-Seizure treatments. The early Post-Traumatic Seizures, in turn, are a contributing factor to ongoing neuropathology, and it is critically important to control these Seizures. Many of the available anti-Seizure drugs target gamma-aminobutyric acid (GABAA) receptors. The inhibitory activity of GABAA receptor activation depends on low intracellular Cl−, which is achieved by the opposing regulation of Na+–K+–Cl− cotransporter 1 (NKCC1) and K+–Cl−–cotransporter 2 (KCC2). Up-regulation of NKCC1 in neurons has been shown to be involved in neonatal Seizures and in ammonia toxicity-induced Seizures. Here, we report that TBI-induced up-regulation of NKCC1 and increased intracellular Cl− concentration. Genetic deletion of NKCC1 or pharmacological inhibition of NKCC1 with bumetanide suppresses TBI-induced Seizures. TGFβ expression was also increased after TBI and competitive antagonism of TGFβ reduced NKKC1 expression, ameliorated reactive astrocytosis, and inhibited Seizures. Thus, TGFβ might be an important pathway involved in NKCC1 up-regulation after TBI. Our findings identify neuronal up-regulation of NKCC1 and its mediation by TGFβ, as a potential and important mechanism in the early Post-Traumatic Seizures, and demonstrate the therapeutic potential of blocking this pathway.
Geoffrey T Manley - One of the best experts on this subject based on the ideXlab platform.
-
aquaporin 4 reduces post traumatic Seizure susceptibility by promoting astrocytic glial scar formation in mice
Journal of Neurotrauma, 2011Co-Authors: Zsolt Zador, Jinghua Yao, Farbod Fazlollahi, Geoffrey T ManleyAbstract:Seizures are important neurologic complications following traumatic brain injury (TBI) and are reported for up to 50% of patients with TBI. Despite several studies, no drug strategy has been able to alter the biological events leading to epileptogenesis. The glial water channel aquaporin-4 (AQP4) was shown to facilitate cytotoxic cell swelling in ischemia and glial scar formation following stab wound injury. In this study, we examined Post-Traumatic Seizure susceptibility of AQP4-deficient mice (AQP4-/-) after injection of pentylenetetrazole (PTZ) 1 month after controlled cortical impact (CCI) and compared them to wild-type sham injury controls. After PTZ injection, AQP4-/- mice demonstrated dramatically shortened Seizure latency (120 ± 40 seconds vs. 300 ± 70 seconds, p < 0.001) and increased Seizure severity (grade 7.5 ± 0.4 vs. 5.8 ± 0.4, p < 0.001) compared to their wild-type counterparts. Morphometric analysis demonstrated a significant two-fold reduction in astrocytosis with concomitant increase in ...
Zsolt Zador - One of the best experts on this subject based on the ideXlab platform.
-
aquaporin 4 reduces post traumatic Seizure susceptibility by promoting astrocytic glial scar formation in mice
Journal of Neurotrauma, 2011Co-Authors: Zsolt Zador, Jinghua Yao, Farbod Fazlollahi, Geoffrey T ManleyAbstract:Seizures are important neurologic complications following traumatic brain injury (TBI) and are reported for up to 50% of patients with TBI. Despite several studies, no drug strategy has been able to alter the biological events leading to epileptogenesis. The glial water channel aquaporin-4 (AQP4) was shown to facilitate cytotoxic cell swelling in ischemia and glial scar formation following stab wound injury. In this study, we examined Post-Traumatic Seizure susceptibility of AQP4-deficient mice (AQP4-/-) after injection of pentylenetetrazole (PTZ) 1 month after controlled cortical impact (CCI) and compared them to wild-type sham injury controls. After PTZ injection, AQP4-/- mice demonstrated dramatically shortened Seizure latency (120 ± 40 seconds vs. 300 ± 70 seconds, p < 0.001) and increased Seizure severity (grade 7.5 ± 0.4 vs. 5.8 ± 0.4, p < 0.001) compared to their wild-type counterparts. Morphometric analysis demonstrated a significant two-fold reduction in astrocytosis with concomitant increase in ...
Coleen M Atkins - One of the best experts on this subject based on the ideXlab platform.
-
post traumatic Seizure susceptibility is attenuated by hypothermia therapy
European Journal of Neuroscience, 2010Co-Authors: Coleen M Atkins, Jessie S Truettner, George Lotocki, Juliana Sanchezmolano, Yuan Kang, Ofelia F Alonso, Thomas J Sick, Dalton W Dietrich, Helen M BramlettAbstract:Traumatic brain injury (TBI) is a major risk factor for the subsequent development of epilepsy. Currently, chronic Seizures after brain injury are often poorly controlled by available antiepileptic drugs. Hypothermia treatment, a modest reduction in brain temperature, reduces inflammation, activates pro-survival signaling pathways, and improves cognitive outcome after TBI. Given the well-known effect of therapeutic hypothermia to ameliorate pathological changes in the brain after TBI, we hypothesized that hypothermia therapy may attenuate the development of Post-Traumatic epilepsy and some of the pathomechanisms that underlie Seizure formation. To test this hypothesis, adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury, and were then maintained at normothermic or moderate hypothermic temperatures for 4 h. At 12 weeks after recovery, Seizure susceptibility was assessed by challenging the animals with pentylenetetrazole, a GABA(A) receptor antagonist. Pentylenetetrazole elicited a significant increase in Seizure frequency in TBI normothermic animals as compared with sham surgery animals and this was significantly reduced in TBI hypothermic animals. Early hypothermia treatment did not rescue chronic dentate hilar neuronal loss nor did it improve loss of doublecortin-labeled cells in the dentate gyrus post-Seizures. However, mossy fiber sprouting was significantly attenuated by hypothermia therapy. These findings demonstrate that reductions in Seizure susceptibility after TBI are improved with Post-Traumatic hypothermia and provide a new therapeutic avenue for the treatment of Post-Traumatic epilepsy.