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Matrix metalloproteinases and diseases of the central nervous system with a special emphasis on ischemic brain
Yvan Gasche1, Paola Marina Soccal, Michiko Kanemitsu
1Department of Fundamental Neuroscience, Geneva University Hospital, Geneva Medical School, 1211 Geneva, Switzerland. yvan.gasche@medecine.unige.ch
Abstract:
Matrix metalloproteinases (MMPs) are involved in the pathogenesis of several diseases of the CNS, that share common pathophysiological processes, such as blood-brain barrier (BBB) disruption, oxidative stress, remodeling of the extracellular matrix (ECM) and inflammation. In ischemic brain injury, MMPs are implicated in various stages of the disease. Early after the onset of ischemia, MMPs contribute to the disruption of the BBB leading to vasogenic edema and to the influx of leucocytes into the CNS. The ability of MMPs to digest the basal lamina of capillaries increases the risk of hemorrhagic transformation of the ischemic tissue. During the acute ischemic phase, maintenance of the ECM is essential for neuronal survival. However, ECM degradation and its reconstitution are critical to tissue recovery. MMPs as a key modulator of ECM homeostasis play a role in the cascades leading to neuronal cell death and tissue regeneration. This pleiotropic implication of MMPs in brain injury has open new areas of investigation, which should lead to innovative therapeutic strategies. Yet MMPs may have a detrimental or beneficial role depending on the stage of brain injury. Simple therapeutic strategies based on MMP inhibition have thus little chance to favorably alter prognosis.
Insights
Matrix metalloproteinases (MMPs) impact central nervous system (CNS) diseases by affecting the blood-brain barrier and extracellular matrix. Their role in brain injury is complex, presenting both detrimental and beneficial effects depending on the disease stage.
Area of Science:
- Neuroscience
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) are crucial enzymes implicated in the pathogenesis of central nervous system (CNS) diseases.
- Common pathophysiological processes in CNS diseases include blood-brain barrier (BBB) disruption, oxidative stress, extracellular matrix (ECM) remodeling, and inflammation.
Purpose of the Study:
- To investigate the multifaceted role of MMPs in the various stages of ischemic brain injury.
- To explore the implications of MMPs in neuronal cell death and tissue regeneration.
- To identify potential innovative therapeutic strategies targeting MMPs.
Main Methods:
- The study reviews the involvement of MMPs in ischemic brain injury based on existing literature.
- Analysis of MMPs' functions in BBB disruption, ECM remodeling, and inflammatory responses.
- Evaluation of MMPs' dual role in neuronal survival, cell death, and tissue recovery.
Main Results:
- MMPs contribute to BBB disruption and vasogenic edema early in ischemic brain injury.
- MMP activity can increase the risk of hemorrhagic transformation in ischemic tissues.
- MMPs play a critical role in ECM degradation and reconstitution, influencing both neuronal cell death and tissue regeneration.
Conclusions:
- MMPs exhibit pleiotropic effects in brain injury, acting as key modulators of ECM homeostasis.
- The role of MMPs (detrimental or beneficial) is highly dependent on the specific stage of brain injury.
- Simple MMP inhibition strategies may not be effective due to the complex and stage-dependent functions of MMPs in neurological disorders.
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