Traumatic brain injury (TBI) currently contributes to nearly 30% of all injury deaths in the United States. Characterized by an abrasive head injury that interrupts normal brain function, TBI can range from mild to severe. Mild symptoms can present themselves as excessive tiredness, difficulty concentrating and lack of clear thinking. Severe cases of TBI are hallmarked by unusual behavior, seizures and loss of consciousness. Research has shown that on a molecular level TBI triggers various mechanisms of cell death alongside attempted tissue recovery, therefore Choi et al sought out to test the treatment of carbon monoxide on rescuing the effects of TBI. Their article titled “Dual effects of carbon monoxide on pericytes and neurogenesis in traumatic brain injury” tests the effects of CO-releasing molecular 3 (CORM-3) and N-tert-butyl-a-phenylnitrone (PBN) on a mouse model of controlled cortical impact TBI.
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HIF-1 alpha Antibody (H1alpha67) [NB100-105] - Analysis of HIF-1 alpha in human hepatocytes from cancer patient using anti-HIF-1 alpha antibody.
Choi et al used a variety of experimental techniques to conduct their experiments to test the effects of CORM-3 and PBN on TBI, including immunohistochemistry, western blot, cell culture, transfections and a series of behavioral tests on the mice. The behavioral tests used were the Morris water maze test to assess spatial learning, the Corner test to asses sensorimotor function, the Grid walk test to monitor frontal lobe behavior and lastly the Neurological severity score (NSS) to quantify motor function and reflexes. Immunostaining was performed to reveal that pericyte cell death occurred 3 days after TBI. Specifically, cells positive for a PDGFR-beta antibody (pericyte marker platelet derived growth factor receptor) co-localized with a cleaved caspase-3 antibody staining. Furthermore, a HIF-1 alpha antibody was used to show subsequent co-localization with cleaved caspase-3 and PDGFR-beta. All experiments were performed using untreated TBI tissue and an actin loading control (for western blot specifically). Statistical analysis on cell counts and densitometry were subject to a one-way ANOVA and Tukey’s test.
Choi et al had significant findings in their research on the effects of both CORM-3 and PBN treatment post TBI. After discovering that pericytes expressed cleaved caspase-3 and HIF-1 alpha 3 days post TBI, they sought to determine whether pericyte injury could be targeted with CO therapy. Mice were administered either saline or CORM-3 1 hour post TBI and pericyte injury was subsequently assessed for 28 days. In addition, CO gas was administered via inhalation. The results showed that both CORM-3 and CO gas exposure reduced the number of cleaved caspase 3/PDGFR-beta positive cells. Likewise, in oxygen deprived human brain pericyte cell cultures, HIF-1 alpha and cleaved caspase 3 were expressed. Introduction to CORM-3 also blocked the induction of these pathways (PBN treatment had a similar effect). Their experiments also showed that CORM-3 treatment reduced the vascular effects of TBI and functional behavior problems after TBI as well. This improvement in behavior included, but was not limited to, improved long term memory and efficiency on the corner test.
Overall these findings made a very strong argument for the successful treatment of cortical TBI, as well as further elucidate the role of hypoxia in the pathology of TBI. In fact, hypoxia reoxygenation treatment could even go as far as to modulate neural stem cell differentiation to ameliorate neurogenesis post TBI. Novus Biologicals carries an extensive catalog of Neuroscience antibodies and HIF-1 antibodies to conduct further research on similar topics.
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References:
Yoon Kyung Choi, Takakuni Maki, Emiri T Mandeville, Seong-Ho Koh, Kazuhide Hayakawa, Ken Arai, Young-Myeong Kim, Michael J Whalen, Changhong Xing, Xiaoying Wang, Kyu-Won Kim & Eng H Lo. Dual effects of carbon monoxide on pericytes and neurogenesis in traumatic brain injury. [PMID: 27668935]
