Effect of focal mild hypothermia on expression of MMP-9, TIMP-1, Tau-1 and β-APP in rats with cerebral ischaemia/reperfusion injury

Abstract

Primary objective: Following stroke, hypothermia is reported to reduce both cellular and extracellular damage. This study aimed to examine the effects of focal mild hypothermia on proteins associated with both extracellular (matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP-9 (TIMP-1)) and cellular damage (Tau-1 and β-amyloid precursor protein (β-APP)) to characterize the protective effects of hypothermia.

Methods and procedures: Male Wistar rats received ischaemic damage using a transient, focal ischaemia/reperfusion model. Afterwards, one group (HT) received 6 hours of focal mild hypothermia (33 °C) applied to the head, while another remained at normal temperature (NT). The brains were collected at 6, 12, 24, 48 and 72 hours after hypothermia to measure infarct volume ratio and to detect cells immunopositive for MMP-9, TIMP-1, Tau-1 and β-APP, while neurological deficits were examined separately after 2 weeks.

Main outcomes and results: Focal mild hypothermia had no effect on infarct volume ratio but expression of MMP-9, TIMP-1 Tau-1 and β-APP was decreased. Furthermore, neurological function in the HT group was better than in the NT group.

Conclusions: Focal mild hypothermia has protective effects on cerebral ischaemia-reperfusion injury characterized by decreased expression of MMP-9, TIMP-1, Tau-1 and β-APP, along with improvement of neurological function despite no changes in infarct volume.

• Amyloid precursor protein
• cerebral ischaemia-reperfusion
• matrix metalloproteinase-9
• mild hypothermia
• rat
• tau-1
• tissue inhibitor of MMP-1