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(Stroke. 2003;34:2171.)
© 2003 American Heart Association, Inc.

Original Contributions

Editorial Comment—Cooling Matrix Metalloproteinases to Improve Thrombolysis in Acute Ischemic Stroke

Neurovascular Research Laboratory, Stroke Unit, Vall d’Hebron Hospital, Barcelona, Spain

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Although their history is only recent, the role of matrix metalloproteinases (MMPs) in ischemic stroke first began to be understood when MMP expression was found to be significantly increased and implicated in blood brain barrier (BBB) disruption, edema formation, and hemorrhagic transformation in animal models of cerebral ischemia.¹ Further study demonstrated the pharmacological blocking of these enzymes and the development of an MMP-9 knockout model, showing reduced infarct volumes and confirming its deleterious role.² Recently, the participation of MMP-9 has also been demonstrated in vivo after human stroke and shown to be related to neurological worsening, infarct size, and hemorrhagic transformation.^3,4

Two innovative points are raised by Horstmann et al⁵: first, the global study of several MMPs, together with their inhibitors and substrates, making their deleterious role more comprehensive; and second, the modification of their temporal profiles regarding different acute stroke treatments.

Concomitant with the increase in MMP-9, Horstmann et al report an increase in laminin breakdown products. This points to proteolytic degradation of critical BBB components by MMP-9, possibly explaining its deleterious role through dissolution of the basal lamina (BL). The BL matrix is constructed from type IV collagen chains and a second polymer network derived from laminin. Entactin connects both complexes, and fibronectin connects the BL with the surrounding tissue and the extracellular matrix. Parallel losses of these BL components have been shown to contribute to loss of brain microvascular integrity⁶ and are now demonstrated in human stroke.

Regarding natural MMP inhibitors, a more decisive role was . . . [Full Text of this Article]

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