Rosiglitazone infusion therapy following minimally invasive surgery for intracerebral hemorrhage evacuation decreases matrix metalloproteinase-9 and blood-brain barrier disruption in rabbits

BMC Neurol. 2015 Mar 17:15:37. doi: 10.1186/s12883-015-0287-3.

Abstract

Background: The objective of this study was to investigate the effects of Rosiglitazone (RSG) infusion therapy following minimally invasive surgery (MIS) for intracerebral hemorrhage(ICH) evacuation on perihematomal secondary brain damage as assessed by MMP-9 levels, blood-brain barrier (BBB) permeability and neurological function.

Methods: A total of 40 male rabbits (2.8-3.4 kg) was randomly assigned to a normal control group (NC group; 10 rabbits), a model control group (MC group; 10 rabbits), a minimally invasive treatment group (MIS group; 10 rabbits) or a combined MIS and RSG group (MIS + RSG group; 10 rabbits). ICH was induced in all the animals, except for the NC group. MIS was performed to evacuate ICH 6 hours after the successful preparation of the ICH model in the MIS and MIS + RSG groups. The animals in the MC group underwent the same procedures for ICH evacuation but without hematoma aspiration, and the NC group was subjected to sham surgical procedures. The neurological deficit scores (Purdy score) and ICH volumes were determined on days 1, 3 and 7. All of the animals were sacrificed on day 7, and the perihematomal brain tissue was removed to determine the levels of PPARγ, MMP-9, BBB permeability and brain water content (BWC).

Results: The Purdy score, perihematomal PPARγ levels, BBB permeability, and BWC were all significantly increased in the MC group compared to the NC group. After performing the MIS for evacuating the ICH, the Purdy score and the ICH volume were decreased on days 1, 3 and 7 compared to the MC group. A remarkable decrease in perihematomal levels of PPARγ, MMP-9, BBB permeability and BWC were observed. The MIS + RSG group displayed a remarkable increase in PPARγ as well as significant decrease in MMP-9, BBB permeability and BWC compared with the MIS group.

Conclusions: RSG infusion therapy following MIS for ICH treatment might be more efficacious for reducing the levels of MMP-9 and secondary brain damage than MIS therapy alone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / metabolism
  • Brain / drug effects
  • Brain / metabolism
  • Brain Injuries / physiopathology
  • Cerebral Hemorrhage / drug therapy*
  • Cerebral Hemorrhage / surgery*
  • Disease Models, Animal
  • Hematoma / drug therapy
  • Hypoglycemic Agents / administration & dosage
  • Infusions, Intraventricular
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Minimally Invasive Surgical Procedures / methods*
  • PPAR gamma / metabolism
  • Permeability
  • Rabbits
  • Random Allocation
  • Rosiglitazone
  • Thiazolidinediones / administration & dosage*

Substances

  • Hypoglycemic Agents
  • PPAR gamma
  • Thiazolidinediones
  • Rosiglitazone
  • Matrix Metalloproteinase 9