Minocycline improves functional outcomes, memory deficits, and histopathology after endovascular perforation-induced subarachnoid hemorrhage in rats

Prativa Sherchan, Tim Lekic, Hidenori Suzuki, Yu Hasegawa, William Rolland, Kamil Duris, Yan Zhan, Jiping Tang, John H. Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)2503-2512
Number of pages10
JournalJournal of Neurotrauma
Volume28
Issue number12
DOIs
StatePublished - Dec 9 2011

ASJC Scopus Subject Areas

  • Clinical Neurology

Keywords

  • endovascular perforation
  • histopathology
  • long-term neurobehavior
  • minocycline
  • subarachnoid hemorrhage
  • Endovascular Procedures/adverse effects
  • Injections, Intraperitoneal
  • Minocycline/administration & dosage
  • Rats
  • Male
  • Random Allocation
  • Rats, Sprague-Dawley
  • Recovery of Function/drug effects
  • Cerebral Arteries/injuries
  • Memory Disorders/drug therapy
  • Animals
  • Subarachnoid Hemorrhage/drug therapy

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