Selective Inhibition of Matrix Metalloproteinase-9 Attenuates Secondary Damage Resulting from Severe Traumatic Brain Injury

Hadass, Orr; Tomlinson, Brittany N.; Gooyit, Major; Chen, Shanyan; Purdy, Justin J.; Walker, Jennifer; Zhang, Chunyang; Giritharan, Andrew; Purnell, Whitley; Robinson, Christopher R.; Shin, Dmitriy; Schroeder, Valerie A.; Suckow, Mark A.; Simonyi, Ágnes; Sun, Grace Y.; Mobashery, Shahriar; Cui, Jiankun; Chang, Mayland; Z, Gu

doi:10.1371/journal.pone.0076904

Cited by 98 publications

(96 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since a role for PrP C in memory impairment is known (Gimbel et al 2010; Chung et al 2010), degradation-resistant Fg-PrP C complex could be involved in short-term memory impairment seen the present study. Recent data indicating a possible role of MMP-9 activity on memory loss after sever TBI (Hadass et al 2013) confirm results of the present study. Lesser changes in memory after mild CCI in Mmp9 −/− mice can be a result of lesser cerebrovascular permeability to Fg, which leads to a lesser accumulation of Fg in SEM and lesser formation of Fg-PrP C complex.…”

Section: Discussionsupporting

confidence: 92%

Ablation of matrix metalloproteinase-9 gene decreases cerebrovascular permeability and fibrinogen deposition post traumatic brain injury in mice

et al. 2014

View full text Add to dashboard Cite

Traumatic brain injury (TBI) is accompanied with enhanced matrix metalloproteinase-9 (MMP-9) activity and elevated levels of plasma fibrinogen (Fg), which is a known inflammatory agent. Activation of MMP-9 and increase in blood content of Fg (i.e. hyperfibrinogenemia, HFg) both contribute to cerebrovascular disorders leading to blood brain barrier disruption. It is well-known that activation of MMP-9 contributes to vascular permeability. It has been shown that at an elevated level (i.e. HFg) Fg disrupts blood brain barrier. However, mechanisms of their actions during TBI are not known. Mild TBI was induced in wild type (WT, C57BL/6J) and MMP-9 gene knockout (Mmp9−/−) homozygous, mice. Pial venular permeability to fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA) in pericontusional area was observed 14 days after injury. Mice memory was tested with a novel object recognition test. Increased expression of Fg endothelial receptor intercellular adhesion protein-1 and formation of caveolae were associated with enhanced activity of MMP-9 causing an increase in pial venular permeability. As a result, an enhanced deposition of Fg and cellular prion protein (PrPC) were found in pericontusional area. These changes were attenuated in Mmp9−/− mice and were associated with lesser loss of short-term memory in these mice than in WT mice. Our data suggest that mild TBI-induced increased cerebrovascular permeability enhances deposition of Fg-PrPC and loss of memory, which is ameliorated in the absence of MMP-9 activity. Thus, targeting MMP-9 activity and blood level of Fg can be a possible therapeutic remedy to diminish vasculo-neuronal damage after TBI.

show abstract

Section: Discussionsupporting

confidence: 92%

Ablation of matrix metalloproteinase-9 gene decreases cerebrovascular permeability and fibrinogen deposition post traumatic brain injury in mice

et al. 2014

View full text Add to dashboard Cite

show abstract

“…43 Therefore, the ability of COG1410 to reduce vasogenic edema and its effects on the vestbulomotor function test demonstrate the potential for this apoE peptide to alter important aspects of neuronal function following TBI. The neuroprotection provided by COG1410 administration after TBI in our study is consistent with previous work reporting that COG1410 reduced the behavioral deficits in different animal models of TBI.…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein E-Mimetic COG1410 Reduces Acute Vasogenic Edema following Traumatic Brain Injury

Cao

Jiang

et al. 2016

Journal of Neurotrauma

View full text Add to dashboard Cite

The degree of post-traumatic brain edema and dysfunction of the blood-brain barrier (BBB) influences the neurofunctional outcome after a traumatic brain injury (TBI). Previous studies have demonstrated that the administration of apolipoprotein E-mimetic peptide COG1410 reduces the brain water content after subarachnoid hemorrhage, intra-cerebral hemorrhage, and focal brain ischemia. However, the effects of COG1410 on vasogenic edema following TBI are not known. The current study evaluated the effects of 1 mg/kg daily COG1410 versus saline administered intravenously after a controlled cortical impact (CCI) injury on BBB dysfunction and vasogenic edema at an acute stage in mice. The results demonstrated that treatment with COG1410 suppressed the activity of matrix metalloproteinase-9, reduced the disruption of the BBB and Evans Blue dye extravasation, reduced the TBI lesion volume and vasogenic edema, and decreased the functional deficits compared with mice treated with vehicle, at an acute stage after CCI. These findings suggest that COG1410 is a promising preclinical therapeutic agent for the treatment of traumatic brain injury.

show abstract

“…Similar phenomena was observed in TBI models that increase in the pro-MMP-9 level was also observed in the lesioned cortex within 24 h after TBI in addition to the up-regulation of activated MMP-9. 49 Moreover, the pro-MMP-9 levels in the lesioned cortex remained elevated for even 10 d after TBI. Early investigation also revealed that pro-MMP-9 levels are elevated as early as 3 h after trauma.…”

Section: Effect Of Sb-3ct On Tbi Prognosismentioning

confidence: 96%

MMP-9 Inhibitor SB-3CT Attenuates Behavioral Impairments and Hippocampal Loss after Traumatic Brain Injury in Rat

Feng

Yin

Gao

et al. 2014

Journal of Neurotrauma

View full text Add to dashboard Cite

The aim of this study was to evaluate the potential efficacy of SB-3CT, a matrix metallopeptidase 9 inhibitor, on behavioral and histological outcomes after traumatic brain injury (TBI) in rats. Adult male Sprague-Dawley rats were randomly divided into three groups (n = 15/group): TBI with SB-3CT treatment, TBI with saline, and sham injury. The TBI model was induced by a fluid percussion TBI device. SB-3CT (50 mg/kg in 10% dimethyl sulfoxide) was administered intraperitoneally at 30 min, 6 h, and 12 h after the TBI. Motor function (beam-balance/beam-walk tests) and spatial learning/memory (Morris water maze) were assessed on post-operative Days 1 -5 and 11-15, respectively. Fluoro-Jade staining, immunofluorescence, and cresyl violet-staining were carried out for histopathological evaluation at 24 h, 72 h, and 15 days after TBI, respectively. It was shown that TBI can result in significant behavioral deficit induced by acute neurodegeneration, increased expression of cleaved caspase-3, and long-term neuronal loss. SB-3CT intervention via the current regime provides robust behavioral protection and hippocampal neurons preservation from the deleterious effects of TBI. Hence, the efficacy of SB-3CT on TBI prognosis could be ascertained. It is believed that the current study adds to the growing literature in identifying SB-3CT as a potential therapy for human brain injury.

show abstract

Selective Inhibition of Matrix Metalloproteinase-9 Attenuates Secondary Damage Resulting from Severe Traumatic Brain Injury

Cited by 98 publications

References 48 publications

Ablation of matrix metalloproteinase-9 gene decreases cerebrovascular permeability and fibrinogen deposition post traumatic brain injury in mice

Ablation of matrix metalloproteinase-9 gene decreases cerebrovascular permeability and fibrinogen deposition post traumatic brain injury in mice

Apolipoprotein E-Mimetic COG1410 Reduces Acute Vasogenic Edema following Traumatic Brain Injury

MMP-9 Inhibitor SB-3CT Attenuates Behavioral Impairments and Hippocampal Loss after Traumatic Brain Injury in Rat

Contact Info

Product

Resources

About