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Review
. 2016 Nov;53(9):6106-6123.
doi: 10.1007/s12035-015-9520-8. Epub 2015 Nov 5.

Role of Matrix Metalloproteinases in the Pathogenesis of Traumatic Brain Injury

P M Abdul Muneer  1 , Bryan J Pfister  2 , James Haorah  2 , Namas Chandra  2
Affiliations
Review

Role of Matrix Metalloproteinases in the Pathogenesis of Traumatic Brain Injury

P M Abdul Muneer et al. Mol Neurobiol. 2016 Nov.

Abstract

Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Studies revealed that the pathogenesis of TBI involves upregulation of MMPs. MMPs form a large family of closely related zinc-dependent endopeptidases, which are primarily responsible for the dynamic remodulation of the extracellular matrix (ECM). Thus, they are involved in several normal physiological processes like growth, development, and wound healing. During pathophysiological conditions, MMPs proteolytically degrade various components of ECM and tight junction (TJ) proteins of BBB and cause BBB disruption. Impairment of BBB causes leakiness of the blood from circulation to brain parenchyma that leads to microhemorrhage and edema. Further, MMPs dysregulate various normal physiological processes like angiogenesis and neurogenesis, and also they participate in the inflammatory and apoptotic cascades by inducing or regulating the specific mediators and their receptors. In this review, we explore the roles of MMPs in various physiological/pathophysiological processes associated with neurological complications, with special emphasis on TBI.

Keywords: Blood-brain barrier; Edema; Extracellular matrix; Hemorrhage; Matrix metalloproteinases; Neurodegeneration; Neuroinflammation; Traumatic brain injury.

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Figures

Fig. 1
Fig. 1
Schematic representation of the role of MMPs in traumatic brain injury. Brain injury activates the expression of MMPs either directly or via other mediators like oxidative stress (reactive oxygen species, ROS). MMPs exacerbate the inflammatory cascades by activating inflammatory cytokines such as IL-1β and TNF-α. MMPs degrade ECM proteins and tight junction proteins of BBB lead to BBB disruption. In addition, MMPs involve in neurodegeneration by activating cell death inducing caspase enzymes and causing apoptosis. Similarly, MMPs induce cellular and vasogenic edema during brain injury
Fig. 2
Fig. 2
Activation of MMP-2 in mild traumatic brain injury: Immunofluorescent staining of MMP2 in rat brain cortex of primary blast (123-kPa peak overpressure) induced mTBI [32] (a) and mild fluid percussion injury (15 psi) and compared with control (b). Scale bar (yellow bar in the last panel)=20 μm in all panels
See this image and copyright information in PMC

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