Matrix metalloproteinase-9 (MMP-9) expression and extracellular signal-regulated kinase 1 and 2 (ERK1/2) activation in exercise-reduced neuronal apoptosis after stroke

Chaudhry, Khawar; Rogers, Ryan; Guo, Miao; Lai, Quirino; Goel, Gunjan; Liebelt, Brandon D.; Ji, Xunming; Curry, Alecia; Carranza, Aaron; Jimenez, David F.; Ding, Yuchuan

doi:10.1016/j.neulet.2010.03.020

Cited by 53 publications

(48 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, following ischemic injury, neuronal apoptosis was seen to be reduced in association with decreased levels of MMP-9 expression in exercise preconditioned rats (Chaudhry et al, 2010). Following pharmacologic inhibition of both ERK1/2 and MMP-9, similar effects were also seen, resulting in less neuronal apoptosis and better neurologic outcomes; however, when only ERK1/2 was inhibited, MMP expression returned to the level of non-exercised control rats, suggesting a pathway involving regulation by ERK1/2 and TNF-α of MMP-9 expression (Chaudhry et al, 2010). ERK1/2 has previously been shown to also work through upregulation of tissue inhibitors of metalloproteinases (TIMPs) (Tong et al, 2004), and TIMPs have been previously shown to be upregulated following chronic exercise in association with decreased MMP-9 levels (Guo et al, 2008a).…”

Section: Blood Brain Barrier Integritymentioning

confidence: 48%

“…These gradual changes are seen following exercise training, in which gradual upregulation of TNF-α and ERK1/2 lead to decreased levels of MMP-9 expression, which also correlates with better outcomes following ischemia/reperfusion injury (Chaudhry et al, 2010). In this study, following ischemic injury, neuronal apoptosis was seen to be reduced in association with decreased levels of MMP-9 expression in exercise preconditioned rats (Chaudhry et al, 2010). Following pharmacologic inhibition of both ERK1/2 and MMP-9, similar effects were also seen, resulting in less neuronal apoptosis and better neurologic outcomes; however, when only ERK1/2 was inhibited, MMP expression returned to the level of non-exercised control rats, suggesting a pathway involving regulation by ERK1/2 and TNF-α of MMP-9 expression (Chaudhry et al, 2010).…”

Section: Blood Brain Barrier Integritymentioning

confidence: 99%

“…Interestingly, when these same rats were treated with tumor necrosis factor (TNF)-α antibody or inhibition of extracellular regulated kinase (ERK), MMP-9 levels were not decreased, and the positive effects on neurologic outcome and infarct volume were no longer seen (Curry et al, 2009;Hosomi et al, 2005), suggesting that TNF-α and ERK serve as regulators of MMP expression. Further studies have shown that ERK1/2 mediates a TNF-α induced an increase in MMP-9 expression in the acute setting (Arai et al, 2003), while the gradual increases in TNF-α and ERK1/2 have been shown to decrease MMP-9 expression and lead to decreased neuronal cell death (Chaudhry et al, 2010). These gradual changes are seen following exercise training, in which gradual upregulation of TNF-α and ERK1/2 lead to decreased levels of MMP-9 expression, which also correlates with better outcomes following ischemia/reperfusion injury (Chaudhry et al, 2010).…”

Section: Blood Brain Barrier Integritymentioning

confidence: 99%

“…Further studies have shown that ERK1/2 mediates a TNF-α induced an increase in MMP-9 expression in the acute setting (Arai et al, 2003), while the gradual increases in TNF-α and ERK1/2 have been shown to decrease MMP-9 expression and lead to decreased neuronal cell death (Chaudhry et al, 2010). These gradual changes are seen following exercise training, in which gradual upregulation of TNF-α and ERK1/2 lead to decreased levels of MMP-9 expression, which also correlates with better outcomes following ischemia/reperfusion injury (Chaudhry et al, 2010). In this study, following ischemic injury, neuronal apoptosis was seen to be reduced in association with decreased levels of MMP-9 expression in exercise preconditioned rats (Chaudhry et al, 2010).…”

Section: Blood Brain Barrier Integritymentioning

confidence: 99%

“…Through its beneficial effects on hypertension, lipid profiles, obesity, and diabetes, exercise training has been associated with decreased stroke incidence and better outcomes after stroke (Evenson et al, 1999;Gillum et al, 1996;Hu et al, 2004). Despite risk factor management, exercise has also been shown to provide endogenous neuroprotection, preserving neuronal viability in the setting of ischemia/ reperfusion injury, resulting in decreased infarct volume and improved neurologic recovery (Chaudhry et al, 2010;Curry et al, 2009;Davis et al, 2007;Ding et al, 2004aDing et al, , 2004bDing et al, , 2005Ding et al, , 2006aDing et al, , 2006bGuo et al, 2008a;Liebelt et al, 2010;Zwagerman et al, 2010aZwagerman et al, , 2010b. These beneficial endogenous effects of exercise preconditioning have been seen even after multivariate analysis has controlled for risk factor alterations (Hu et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Mechanisms of Neuroprotection Underlying Physical Exercise in Ischemia - Reperfusion Injury

Dornbos¹,

Ding²

2012

Brain Injury - Pathogenesis, Monitoring, Recovery and Management

Self Cite

View full text Add to dashboard Cite

Mechanisms of Neuroprotection Underlying Physical Exercise in Ischemia -Reperfusion Injury 301 neuroprotection after exercise has stopped.Another study revealed that the neuroprotective effects of exercise preconditioning appear to be long-lasting, showing that 3 weeks after cessation of exercise, rats still maintained lower levels of neurologic deficit and decreased stroke volume when compared to non-exercise rats (Ding et al., 2004b). Future human studies ought to determine the exact duration needed for maximal endogenous neuroprotection. Preconditioning modalitiesWhile various modalities, such as treadmill running, voluntary running, simple and complex exercise, have been shown to provide variable amounts of neuroprotection. When comparing forced exercise on a treadmill to voluntary running on a running wheel, rats forced to exercise on a treadmill tend to have better neurologic outcomes after stroke (Hayes et al., 2008). Previous studies have shown that forced exercise on a treadmill is slower but more constant than voluntary exercise occurs in shorter spurts with faster speed, although the total distance is equal in the two groups (Noble et al., 1999). This neuroprotection in forced exercise subjects led to decreased stroke volume, lessened neurologic deficit, upregulation of heat shock proteins, increased neurogenesis and cerebral metabolism (Hayes et al., 2008;Kinni et al., 2011;Leasure and Jones, 2008). These findings show that moderate exercise over a longer time period conveys more efficient and greater neuroprotection than more vigorous exercise over shorter time periods. In addition to the studies assessing forced and voluntary exercise, differences have also been established when comparing simple and complex exercise. This study analyzed simple exercise as the repetitive movements of treadmill running, whereas complex exercise constituted enriched activities which required both balance and coordination (Ding et al., 2003). Following ischemia/reperfusion injury, rats preconditioned with complex exercise demonstrated increased synaptogenesis and improved neurologic outcomes when compared to simple treadmill exercise (Ding et al., 2003;Jones et al., 1999). Simple exercise training also alleviates much of the injury following ischemia/reperfusion, but its benefit is less pronounced than what is observed with complex exercise training. Although no human studies have definitively shown the most effective means of exercise for enhanced neuroprotection, these animal studies provide a solid framework for the development of appropriate exercise regimens. Moderate exercise intensity, including components of balance, coordination and stress, taking place over a sustained duration seem to be the most neuroprotective when compared to other exercise modalities and intensities.

show abstract