TY - JOUR
T1 - Minocycline improves functional outcomes, memory deficits, and histopathology after endovascular perforation-induced subarachnoid hemorrhage in rats
AU - Sherchan, Prativa
AU - Lekic, Tim
AU - Suzuki, Hidenori
AU - Hasegawa, Yu
AU - Rolland, William
AU - Duris, Kamil
AU - Zhan, Yan
AU - Tang, Jiping
AU - Zhang, John H.
N1 - Prativa Sherchan, 1 Tim Lekic, 1 Hidenori Suzuki, 1 Yu Hasegawa, 1 William Rolland, 1 Kamil Duris, 1 Yan Zhan, 1 Jiping Tang, 1 and John H. Zhang 1,, 2,, 3 Subarachnoid hemorrhage (SAH) results in significant long-lasting cognitive dysfunction. Therefore, evaluating acute and long-term outcomes after therapeutic intervention is important for clinical translation.
PY - 2011/12/9
Y1 - 2011/12/9
N2 - Subarachnoid hemorrhage (SAH) results in significant long-lasting cognitive dysfunction. Therefore, evaluating acute and long-term outcomes after therapeutic intervention is important for clinical translation. The aim of this study was to use minocycline, a known neuroprotectant agent, to evaluate the long-term benefits in terms of neurobehavior and neuropathology after experimental SAH in rats, and to determine which neurobehavioral test would be effective for long-term evaluation. SAH was induced by endovascular perforation in adult male Sprague-Dawley rats (n=118). The animals were treated with intraperitoneal injection of minocycline (45 mg/kg or 135 mg/kg) or vehicle 1 h after SAH induction. In the short-term, animals were euthanized at 24 and 72 h for evaluation of neurobehavior, brain water content, and matrix metalloproteinase (MMP) activity. In the long-term, neurobehavior was evaluated at days 21-28 post-SAH, and histopathological analysis was done at day 28. High-dose but not low-dose minocycline reduced brain water content at 24 h, and therefore only the high-dose regimen was used for further evaluation, which reduced MMP-9 activity at 24 h. Further, high-dose minocycline improved spatial memory and attenuated neuronal loss in the hippocampus and cortex. The rotarod, T-maze, and water maze tests, but not the inclined plane test, detected neurobehavioral deficits in SAH rats at days 21-28. This study demonstrates that minocycline attenuates long-term functional and morphological outcomes after endovascular perforation-induced SAH. Long-term neurobehavioral assessments using the rotarod, T-maze, and water maze tests could be useful to evaluate the efficacy of therapeutic intervention after experimental SAH. © 2011, Mary Ann Liebert, Inc.
AB - Subarachnoid hemorrhage (SAH) results in significant long-lasting cognitive dysfunction. Therefore, evaluating acute and long-term outcomes after therapeutic intervention is important for clinical translation. The aim of this study was to use minocycline, a known neuroprotectant agent, to evaluate the long-term benefits in terms of neurobehavior and neuropathology after experimental SAH in rats, and to determine which neurobehavioral test would be effective for long-term evaluation. SAH was induced by endovascular perforation in adult male Sprague-Dawley rats (n=118). The animals were treated with intraperitoneal injection of minocycline (45 mg/kg or 135 mg/kg) or vehicle 1 h after SAH induction. In the short-term, animals were euthanized at 24 and 72 h for evaluation of neurobehavior, brain water content, and matrix metalloproteinase (MMP) activity. In the long-term, neurobehavior was evaluated at days 21-28 post-SAH, and histopathological analysis was done at day 28. High-dose but not low-dose minocycline reduced brain water content at 24 h, and therefore only the high-dose regimen was used for further evaluation, which reduced MMP-9 activity at 24 h. Further, high-dose minocycline improved spatial memory and attenuated neuronal loss in the hippocampus and cortex. The rotarod, T-maze, and water maze tests, but not the inclined plane test, detected neurobehavioral deficits in SAH rats at days 21-28. This study demonstrates that minocycline attenuates long-term functional and morphological outcomes after endovascular perforation-induced SAH. Long-term neurobehavioral assessments using the rotarod, T-maze, and water maze tests could be useful to evaluate the efficacy of therapeutic intervention after experimental SAH. © 2011, Mary Ann Liebert, Inc.
KW - endovascular perforation
KW - histopathology
KW - long-term neurobehavior
KW - minocycline
KW - subarachnoid hemorrhage
KW - Endovascular Procedures/adverse effects
KW - Injections, Intraperitoneal
KW - Minocycline/administration & dosage
KW - Rats
KW - Male
KW - Random Allocation
KW - Rats, Sprague-Dawley
KW - Recovery of Function/drug effects
KW - Cerebral Arteries/injuries
KW - Memory Disorders/drug therapy
KW - Animals
KW - Subarachnoid Hemorrhage/drug therapy
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UR - http://www.scopus.com/inward/citedby.url?scp=83455163234&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/3f3c7369-bf71-385f-9ec3-c91185276075/
U2 - 10.1089/neu.2011.1864
DO - 10.1089/neu.2011.1864
M3 - Article
C2 - 22013966
SN - 0897-7151
VL - 28
SP - 2503
EP - 2512
JO - Journal of Neurotrauma
JF - Journal of Neurotrauma
IS - 12
ER -