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

J Neurotrauma. 2011 Dec;28(12):2503-12. doi: 10.1089/neu.2011.1864. Epub 2011 Oct 20.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cerebral Arteries / injuries*
  • Endovascular Procedures / adverse effects*
  • Injections, Intraperitoneal
  • Male
  • Memory Disorders / drug therapy*
  • Memory Disorders / parasitology
  • Memory Disorders / pathology
  • Minocycline / administration & dosage*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects*
  • Recovery of Function / physiology
  • Subarachnoid Hemorrhage / drug therapy*
  • Subarachnoid Hemorrhage / pathology
  • Subarachnoid Hemorrhage / psychology


  • Minocycline