Journal of neurotrauma
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Journal of neurotrauma · Jul 2011
Curcumin attenuates the expression and secretion of RANTES after spinal cord injury in vivo and lipopolysaccharide-induced astrocyte reactivation in vitro.
Curcumin has been proposed for treatment of various neuroinflammatory and neurodegenerative conditions, including post-traumatic inflammation during acute spinal cord injury (SCI). In this study, we examined whether curcumin anti-inflammation involves regulation of astrocyte reactivation, with special focus on the injury-induced RANTES (regulated on expression normal T-cell expressed and secreted) from astrocytes in acute SCI. Male Sprague-Dawley (SD) rats were subjected to impact injury of the spinal cord followed by treatment with curcumin (40 mg/kg i.p.). ⋯ Furthermore, cortical neurons cultured with astrocyte conditioned medium (ACM) conditioned with both LPS and curcumin (LPS-curcumin/ACM), which characteristically exhibited decreased RANTES expression when compared with ACM from astrocytes treated with LPS alone (LPS/ACM), showed higher level of cell viability and lower level of cell death as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction activity assay and lactate dehydrogenase release assay, respectively. Knockdown of RANTES expression by siRNA (siRANTES) shows reduced RANTES expression and release from LPS-reactivated astrocytes, and ACM obtained from this condition (LPS-siRANTES/ACM) becomes less cytotoxic as compared with the LPS-ACM. Therefore, curcumin reduction of robust RANTES production in reactivated astrocytes both in vitro and in vivo may contribute to its neuroprotection and potential application in SCI.
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Journal of neurotrauma · Jul 2011
Cardiovascular responses to static muscle contraction in patients with brachial plexus injury treated with intercostal nerve transfer.
Pressor response is carried in afferent fibers of somatic nerves to increase blood pressure (BP) and heart rate (HR) during static exercise in humans. However, there is no information that peripheral responses restore muscle contraction with nerve transfer operation. In this study, we aimed to assess isometric exercise-induced pressor responses in patients with brachial plexus injury (BPI) after intercostal nerve transfer (ICNT) to restore elbow flexor muscles. ⋯ Isometric static exercise at 35% of MVC did not induce pressor and HR changes on the ICNT side. The difference in the responses between the two sides could have been caused by incomplete recovery of afferent nerve function following nerve repair, despite the restoration of efferent nerve function. Alternatively, the HR and BP responses to static contraction may depend upon the active muscle mass.
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Journal of neurotrauma · Jul 2011
Inhibition of Ras-GTPase farnesylation and the ubiquitin-proteasome system or treatment with angiotensin-(1-7) attenuates spinal cord injury-induced cardiac dysfunction.
Cardiovascular diseases are one of the principal causes of death and disability in people with spinal cord injury (SCI). The present study was designed to investigate if acute treatment with FPTIII (an inhibitor of Ras-GTPase farnesylation) or MG132 (an inhibitor of ubiquitin-proteasome pathway [UPS]) or administration of angiotensin-(1-7), also known as Ang-(1-7), (a known inhibitor of cardiac NF-kB) would be cardioprotective. The weight drop technique produced a consistent contusive injury of the spinal cord at the T13 segment. ⋯ Percent recovery (%R) in P(max) and CF in hearts from control animals were 48±6 and 50±5, respectively, whereas none of the hearts from animals with SCI recovered after 30 min of ischemia. Treatment with FPTIII, MG 132, or Ang-(1-7) before ischemia for 30 min led to significant recovery of heart function following ischemia in SCI-6 but not in SCI-12 animals. Thus we have shown that acute treatments with FPTIII, MG132, or Ang-(1-7) improve cardiac recovery following ischemic insult in animals with SCI and may represent novel therapeutic agents for preventing ischemia-induced cardiac dysfunction in patients with SCI.
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Journal of neurotrauma · Jul 2011
Treatment of TBI with collagen scaffolds and human marrow stromal cells increases the expression of tissue plasminogen activator.
This study examines the effects of combination therapy of collagen scaffolds and human marrow stromal cells (hMSCs) on the expression of tissue plasminogen activator (tPA) after traumatic brain injury (TBI) in rats. Adult male Wistar rats (n=48) were injured with controlled cortical impact and treated either with scaffolds suffused with hMSCs (3×10(6)) or hMSCs (3×10(6)) alone transplanted into the lesion cavity 1 week after TBI. A control group was treated with saline. ⋯ Triple staining showed that more neurons were tPA-positive in the scaffold+hMSC group compared to the other two groups (p<0.05). Western blot analysis and qRT-PCR showed that scaffold+hMSC and hMSC-alone treatment enhanced the expression of tPA compared to controls (p<0.05), but tPA expression was significantly greater in the scaffold+hMSC group. The induction of tPA by hMSCs after TBI may be one of the mechanisms involved in promoting functional improvement after TBI.