Depressed cortical excitability and elevated matrix metalloproteinases in remote brain regions following intracerebral hemorrhage

Mun-Bryce, Sheila; Wilkerson, Arika C; Pacheco, Bernadette; Zhang, Tongsheng; Rai, Seema; Wang, Yaozhi; Okada, Yoshio

doi:10.1016/j.brainres.2004.08.024

Cited by 30 publications

(24 citation statements)

References 39 publications

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“…Extensive brain edema and brain damage could occur in either the perihematomal or remote brain regions after ICH, thus leading to neurological deficits (Qureshi et al 2001;Wagner et al 2003;Mun-Bryce et al 2004;Hua et al 2006;Xi et al 2006). Toxic hematoma extravasations, such as iron (Wagner et al 2003;Nakamura et al 2005;Hua et al 2006;Okauchi et al 2009), inflammatory cytokines, and thrombin (Mun-Bryce et al 2004;Xi et al 2006;Zhang et al 2006), contribute to the occurrence of neurological deficits. Nevertheless, the mechanism of how toxic hematoma extravasations cause the remote effects of ICH is still unknown.…”

Section: Discussionmentioning

confidence: 99%

Intracerebral Hematoma Extends via Perivascular Spaces and Perineurium

Yin

Lü

Qiu

et al. 2013

Tohoku J. Exp. Med.

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Intracerebral hemorrhage (ICH) is a devastating disorder associated with high morbidity and mortality. ICH results in the formation of hematoma that affects not only the primary site of injury but also the remote regions. In fact, hematoma can extend via perivascular spaces (also called Virchow-Robin spaces, VRS) and perineurium in an animal model of ICH. In the present study, we used magnetic resonance imaging (MRI) with susceptibility-weighted imaging (SWI) to investigate the characteristics of the perivascular and perineural extensions of hematomas in patients with ICH. A total of 20 ICH patients without secondary subarachnoid and secondary intraventricular hemorrhages were recruited. Brain MRI scans, including SWI, T1, and T2-weighted images, were performed between 17 h to 7 days after the onset of ICH. MRI with SWI revealed that paramagnetic substances spread along the VRS or the perineurium. Such distribution could cause the formation of cerebral microbleeds (CMBs). However, the distribution of remote hemorrhagic lesions varied, depending on the size and location of the original hematoma. The unenhanced CT scans of the 20 patients did not show any hyperdensity around the blood vessels and nerve tracts outside the hematoma. These results indicate the perivascular and perineural extensions of hematomas in patients with ICH, which is formed by the leakage of the original hematoma via the VRS or perineurium. We also provide a new explanation for the series of pathological processes involved in ICH, including the remote effects of hematoma and the formation of CMBs in patients with ICH.

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Section: Discussionmentioning

confidence: 99%

Intracerebral Hematoma Extends via Perivascular Spaces and Perineurium

Yin

Lü

Qiu

et al. 2013

Tohoku J. Exp. Med.

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“…Interestingly, Mun-Bryce et al [39] used somatic evoked potentials in hemorrhagic stroke to show the depressed cortical response, also contralateral to the hematoma site, which was followed by overexpression of MMP-9 and MMP-2 (gelatinases), implying that neuroinflammation triggered by blood extravasation in the course of ICH is not limited to the directly damaged brain tissue. This may suggest that the inflammation in the course of ICH is not only localized to the lesion but also involves distant areas.…”

Section: What Is the Link Between The Function Of Mmps And The Pathogmentioning

confidence: 99%

Matrix Metalloproteinases in Human Spontaneous Intracerebral Hemorrhage: An Update

et al. 2012

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Background: In default of a plausible and satisfactory causal treatment for hemorrhagic stroke, a role of matrix metalloproteinases (MMPs) in the pathogenesis of cerebrovascular diseases has recently been widely discussed. The well-known impact of MMPs on extracellular matrix destruction triggered by inflammation as a foundation for several diseases, including stroke, is very much in evidence. Newly, some additional aspects of MMP function considering their intracellular activity crucial for neuronal death following ischemic brain damage have emerged. The effect of blood-brain barrier disruption caused by MMPs on the prognosis in patients suffering from spontaneous intracerebral hemorrhage (ICH) has been of interest since it throws a new light upon the pathogenesis, course and possible therapeutic approaches for this least treatable and at the same time most life-threatening form of stroke. Hence, we primarily aimed to review the current clinical knowledge on the significance of metalloproteinase activation in the course of spontaneous intracranial hemorrhage in humans. We also provide a brief characterization of the MMP enzyme family and report on the latest findings on issues arising from experimental studies. Methods: A Medline search using the following key words was performed: matrix metalloproteinases + spontaneous intracerebral hemorrhage/intracranial hemorrhage/bleeding/hemorrhagic stroke. We accepted studies reporting on MMP expression in adult patients with spontaneous ICH, as well as its relation to radiological and clinical features and patients’ outcome. For the final review, 18 clinical studies were considered. MMP inhibition was reviewed on the basis of 11 relevant experimental studies. Also, some relevant reports on the biology of MMPs and their pathophysiology in ICH were reviewed. Results and Conclusions: Many studies provide convincing evidence of a detrimental role of MMPs in ICH, stressing their association with neuroinflammation. The role of MMPs in hemorrhagic stroke appears critical for hematoma and brain edema growth as well as for neuronal death, which are understood as secondary brain injury and may have a considerable clinical impact. Although data on human spontaneous ICH are scarce and mostly based on small populations, they reveal the apparent correlation between MMPs and clinical and radiological ICH features as well as the functional outcome, which might rationalize future therapeutic strategies. However, attempts at MMP inhibition in spontaneous ICH have solely been made under experimental conditions and were associated with a wide range of possible side effects. Therefore, further comprehensive, elucidating investigations in this field are vital before any conclusions could be translated to humans.

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“…However, MMP-9 is currently the most thoroughly studied MMP in the setting of ICH [29,71,91,[93][94][95][96]. MMP-9 is increased early in ICH, and its presence can be found from 48 h to 7 days in both cerebral hemispheres [29] Additionally, deletion of the gene for MMP-9 resulted in upregulation of MMP-2 and -3, which was associated with worse edema, hemorrhage and neurologic deficit [93]. The association of a genetic deficiency of MMP-9 with MMP-2 and -3 is unclear, as is the explanation of poorer clinical outcomes with the absence of MMP-9.…”

Section: Matrix Metalloproteinasesmentioning

confidence: 99%

“…The abundance of white matter in the porcine model makes it particularly relevant, as it is similar to the proportion of white-to-gray matter found in humans. The swine model has been utilized to evaluate changes in somatosensory evoked potential changes after ICH [28], and more recent publications have focused on ICH effects on cortical excitability at anatomic locations distal to the hematoma with or without corpus callosum transection [29][30][31]. With the publication of the Surgical Treatment of ICH (STICH) trial results [32], enthusiasm for surgical treatment has waned, although technological advancements in clot extraction have generated multiple endeavors using the porcine model to evaluate surgical clot removal augmented with tissue plasminogen activator (t-PA) at both hyperacute (less than 6 h) [33] and long-term (10 days) [34] time points.…”

Section: Porcinementioning

confidence: 99%

Preclinical Models of Intracerebral Hemorrhage: A Translational Perspective

2007

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Intracerebral hemorrhage (ICH) is a devastating and relatively common disease affecting as many as 50,000 people annually in the United States alone. ICH remains associated with poor outcome, and approximately 40-50% of afflicted patients will die within 30 days. In reports from the NIH and AHA, the importance of developing clinically relevant models of ICH that will extend our understanding of the pathophysiology of the disease and target new therapeutic approaches was emphasized. Traditionally, preclinical ICH research has most commonly utilized two paradigms: clostridial collagenase-induced hemorrhage and autologous blood injection. In this article, the use of various species is examined in the context of the different model types for ICH, and a mechanistic approach is considered in evaluating the numerous breakthroughs in our current fund of knowledge. Each of the model types has its inherent strengths and weaknesses and has the potential to further our understanding of the pathophysiology and treatment of ICH. In particular, transgenic rodent models may be helpful in addressing genetic influences on recovery from ICH.

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Depressed cortical excitability and elevated matrix metalloproteinases in remote brain regions following intracerebral hemorrhage

Cited by 30 publications

References 39 publications

Intracerebral Hematoma Extends via Perivascular Spaces and Perineurium

Intracerebral Hematoma Extends via Perivascular Spaces and Perineurium

Matrix Metalloproteinases in Human Spontaneous Intracerebral Hemorrhage: An Update

Preclinical Models of Intracerebral Hemorrhage: A Translational Perspective

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