Activated protein C is neuroprotective and mediates new blood vessel formation and neurogenesis after controlled cortical impact
| Autor: | Corey T. Walker, Anthony L. Petraglia, Andrew H. Marky, Berislav V. Zlokovic, Meenakshisundaram Thiyagarajan |
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| Rok vydání: | 2009 |
| Předmět: |
Doublecortin Domain Proteins
Male Pathology medicine.medical_specialty Traumatic brain injury Neurogenesis Subventricular zone Neovascularization Physiologic Vascular Cell Adhesion Molecule-1 Cell Count Pharmacology Motor Activity Neuroprotection Rotarod performance test Article Neovascularization Lesion Mice medicine Animals Cerebral Cortex Analysis of Variance Hand Strength business.industry Neuropeptides medicine.disease Enzyme Activation Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Ki-67 Antigen Neuroprotective Agents Bromodeoxyuridine Brain Injuries Rotarod Performance Test Surgery Neurology (clinical) medicine.symptom business Microtubule-Associated Proteins Psychomotor Performance Blood vessel Protein C |
| Zdroj: | Neurosurgery. 66(1) |
| ISSN: | 1524-4040 |
| Popis: | Objective Activated protein C (APC) is neuroprotective in stroke models and promotes postischemic neovascularization and neurogenesis. We used a controlled cortical impact (CCI) in mice to determine the effects of APC on neuroprotection and angiogenesis and neurogenesis after traumatic brain injury (TBI). Methods Mice were given (1) single-dose APC (0.8 mg/kg intraperitoneally) 15 minutes after injury, (2) multidose APC (0.8 mg/kg intraperitoneally) 15 minutes and 6 to 48 hours after injury, or (3) vehicle. We then assessed the effects of APC on posttraumatic motor function with the rotarod and wire grip and beam balance tasks, and we determined the lesion volumes and studied the formation of new blood vessels and markers of neurogenesis. Results Mice treated with single-dose or multidose APC, compared with vehicle, showed significantly improved motor function on all tests. In the single-dose and multidose APC treatment groups, at 7 days after treatment, lesion volume was significantly decreased by 30% and 50%, respectively. Multidose APC, but not single-dose APC, increased new blood vessel formation as shown by CD105(+)/Ki-67(+) double immunostaining by nearly 2-fold at 7 days. Multidose APC also promoted posttraumatic proliferation of neuroblasts in the subventricular zone (SVZ) and their migration from the SVZ to the perilesional area. Conclusion Activated protein C improves functional outcome and is neuroprotective after TBI. It also promotes angiogenesis and survival and migration of neuroblasts from the SVZ to the perilesional area, but the exact role of these brain repair mechanisms remains to be determined. The present findings suggest that APC therapy may hold a significant therapeutic potential for TBI. |
| Databáze: | OpenAIRE |
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