Microglial activation induced by brain trauma is suppressed by post-injury treatment with a PARP inhibitor
| العنوان: | Microglial activation induced by brain trauma is suppressed by post-injury treatment with a PARP inhibitor |
|---|---|
| المؤلفون: | Jian Shi, Seok Joon Won, Stephen M. Massa, Joana C. D’Avila, Jialing Liu, Deborah Bingham, Tiina M. Kauppinen, Tina I. Lam, Raymond A. Swanson |
| المصدر: | d'Avila, Joana C; Lam, Tina I; Bingham, Deborah; Shi, Jian; Won, Seok; Kauppinen, Tiina M; et al.(2012). Microglial activation induced by brain trauma is suppressed by post-injury treatment with a PARP inhibitor. Journal of Neuroinflammation, 9(1), 31. doi: http://dx.doi.org/10.1186/1742-2094-9-31Test. Retrieved from: http://www.escholarship.org/uc/item/7bw07541Test Journal of Neuroinflammation, Vol 9, Iss 1, p 31 (2012) Journal of Neuroinflammation |
| بيانات النشر: | eScholarship, University of California, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Male, Pathology, Indoles, Time Factors, Hippocampus, Minocycline, Pharmacology, Functional Laterality, lcsh:RC346-429, Rats, Sprague-Dawley, 0302 clinical medicine, Forelimb, Cerebral Cortex, Neurons, 0303 health sciences, CD11b Antigen, Microglia, traumatic brain injury, General Neuroscience, medicine.anatomical_structure, Neurology, Motor Skills, Cerebral cortex, PARP inhibitor, Encephalitis, Poly(ADP-ribose) Polymerases, medicine.symptom, Astrocyte, Injections, Intraperitoneal, medicine.medical_specialty, Cell Survival, Traumatic brain injury, Immunology, Inflammation, Poly(ADP-ribose) Polymerase Inhibitors, Biology, 03 medical and health sciences, Cellular and Molecular Neuroscience, Glial Fibrillary Acidic Protein, medicine, Animals, Behavioral, lcsh:Neurology. Diseases of the nervous system, 030304 developmental biology, Analysis of Variance, Poly(ADP-ribose) polymerase, Research, medicine.disease, Rats, Disease Models, Animal, Gene Expression Regulation, nervous system, Brain Injuries, biology.protein, NeuN, 030217 neurology & neurosurgery |
| الوصف: | Background Traumatic brain injury (TBI) induces activation of microglia. Activated microglia can in turn increase secondary injury and impair recovery. This innate immune response requires hours to days to become fully manifest, thus providing a clinically relevant window of opportunity for therapeutic intervention. Microglial activation is regulated in part by poly(ADP-ribose) polymerase-1 (PARP-1). Inhibition of PARP-1 activity suppresses NF-kB-dependent gene transcription and thereby blocks several aspects of microglial activation. Here we evaluated the efficacy of a PARP inhibitor, INO-1001, in suppressing microglial activation after cortical impact in the rat. Methods Rats were subjected to controlled cortical impact and subsequently treated with 10 mg/kg of INO-1001 (or vehicle alone) beginning 20 - 24 hours after the TBI. Brains were harvested at several time points for histological evaluation of inflammation and neuronal survival, using markers for microglial activation (morphology and CD11b expression), astrocyte activation (GFAP), and neuronal survival (NeuN). Rats were also evaluated at 8 weeks after TBI using measures of forelimb dexterity: the sticky tape test, cylinder test, and vermicelli test. Results Peak microglial and astrocyte activation was observed 5 to 7 days after this injury. INO-1001 significantly reduced microglial activation in the peri-lesion cortex and ipsilateral hippocampus. No rebound inflammation was observed in rats that were treated with INO-1001 or vehicle for 12 days followed by 4 days without drug. The reduced inflammation was associated with increased neuronal survival in the peri-lesion cortex and improved performance on tests of forelimb dexterity conducted 8 weeks after TBI. Conclusions Treatment with a PARP inhibitor for 12 days after TBI, with the first dose given as long as 20 hours after injury, can reduce inflammation and improve histological and functional outcomes. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::03ec6fe5d766e642dbc050e5be361645Test http://www.escholarship.org/uc/item/7bw07541Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....03ec6fe5d766e642dbc050e5be361645 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |