Reduced neurogenesis after suppressed inflammation by minocycline in transient cerebral ischemia in rat

J Neurol Sci. 2009 Apr 15;279(1-2):70-5. doi: 10.1016/j.jns.2008.12.025. Epub 2009 Jan 29.

Abstract

Recently, the beneficial role of minocycline on endogenous neurogenesis after cerebral ischemia has been contradicted by many reports. We examined whether minocycline influences post-ischemic neurogenesis in the subventricular zone. Adult male Sprague-Dawley rats were subjected to focal cerebral ischemia for 2 h, and divided into a minocycline-treated (90 mg/Kg on reperfusion and 45 mg/Kg daily for maintenance) and a saline-treated group. Bromodeoxyuridine was injected to determine levels of cell proliferation. Inflammation was assessed by counting polymorphonuclear cell and activated microglia and by measuring myeloperoxidase activity. Endogenous neurogenesis was quantified by immunohistochemical staining and functional outcome was measured by infarct size and behavioral tests. Minocycline treatment decreased inflammation on 1st and 4th days after ischemia. BrdU-positive cells on 7th day (saline vs. minocycline: 602.80+/-146.96 vs. 399.40+/-109.69) and the number of double labeling cells of BrdU/NeuN on 7th day (13.00+/-4.36 vs. 6.40+/-2.07) and BrdU/DCx on 4th day (17.00+/-5.00 vs. 7.50+/-1.91) were significantly decreased in minocycline-treated rats. Infarct size and behavioral tests were not different. Our results indicate that minocycline may reduce immediate post-ischemic neurogenesis despite adequately suppressed inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Brain / pathology
  • Brain / physiopathology
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / pathology
  • Brain Ischemia / physiopathology
  • Bromodeoxyuridine
  • Cell Count
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Enzyme Activation / drug effects
  • Ischemic Attack, Transient / drug therapy*
  • Ischemic Attack, Transient / pathology
  • Ischemic Attack, Transient / physiopathology
  • Male
  • Microglia / physiology
  • Microtubule-Associated Proteins / metabolism
  • Minocycline / therapeutic use*
  • Motor Activity / drug effects
  • Neurogenesis / drug effects*
  • Neurogenesis / physiology
  • Neuroimmunomodulation / drug effects
  • Neurons / drug effects
  • Neurons / physiology
  • Neuropeptides / metabolism
  • Neutrophils / physiology
  • Peroxidase / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Dcx protein, rat
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Microtubule-Associated Proteins
  • Neuropeptides
  • Peroxidase
  • Minocycline
  • Bromodeoxyuridine