Matrix metalloproteinase 9 inhibition reduces early brain injury in cortex after subarachnoid hemorrhage
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Updated: Jun 6, 2026
Intrastriatal Injection of Autologous Blood or Clostridial Collagenase as Murine Models of Intracerebral Hemorrhage
Published on: July 3, 2014
Zong-duo Guo1, Xiao-dong Zhang, Hai-tao Wu
1Department of Neurosurgery, First Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Abstract:
This study investigated the role of matrix metalloproteinase-9 (MMP-9) in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Sprague-Dawley male rats (n=30) between 250 and 300 g were used. SAH was produced by injecting autologous arterial blood into the prechiasmatic cistern. SB-3CT, a selective MMP-9 inhibitor, was injected intraperitoneally after SAH induction. MMP-9 protein expression was measured by western blot; laminin expression and neuronal cells in the cerebral cortex were studied by immunohistochemistry and TUNEL staining at 24h after SAH. MMP-9 expression was increased after SAH and decreased by SB-3CT inhibition at 24h after SAH (P<0.01). Laminin, the substrate of MMP-9, was decreased at 24h after SAH, and SB-3CT prevented laminin degradation. The number of TUNEL-positive neurons in cerebral cortex was increased after SAH and decreased by SB-3CT (P<0.01). MMP-9 may be involved in EBI after SAH and inhibition of MMP-9 may reduce EBI in cerebral cortex.
Insights
Matrix metalloproteinase-9 (MMP-9) plays a role in early brain injury (EBI) following subarachnoid hemorrhage (SAH). Inhibiting MMP-9 with SB-3CT reduced neuronal damage and protected laminin in the cerebral cortex.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Subarachnoid hemorrhage (SAH) frequently leads to early brain injury (EBI).
- Matrix metalloproteinase-9 (MMP-9) is implicated in the pathophysiology of neurological damage.
- Understanding MMP-9's role in EBI is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the role of MMP-9 in EBI after SAH.
- To evaluate the therapeutic potential of a selective MMP-9 inhibitor, SB-3CT, in mitigating EBI.
Main Methods:
- SAH was induced in Sprague-Dawley rats.
- SB-3CT was administered to inhibit MMP-9.
- MMP-9 and laminin expression were assessed using Western blot and immunohistochemistry.
- Neuronal apoptosis was quantified via TUNEL staining at 24 hours post-SAH.
Main Results:
- MMP-9 expression significantly increased post-SAH and was reduced by SB-3CT.
- Laminin degradation was observed after SAH, and SB-3CT treatment prevented this.
- The number of TUNEL-positive neurons in the cerebral cortex increased post-SAH but decreased with SB-3CT treatment.
Conclusions:
- MMP-9 is involved in the development of EBI following SAH.
- Inhibition of MMP-9 with SB-3CT demonstrates a neuroprotective effect by reducing neuronal apoptosis and preserving the extracellular matrix in the cerebral cortex.
