Stem cell therapy and curcumin synergistically enhance recovery from spinal cord injury.

Acute traumatic spinal cord injury (SCI) is marked by the enhanced production of local cytokines and pro-inflammatory substances that induce gliosis and prevent reinnervation. The transplantation of stem cells is a promising treatment strategy for SCI. In order to facilitate functional recovery, we employed stem cell therapy alone or in combination with curcumin, a naturally-occurring anti-inflammatory component of turmeric (Curcuma longa), which potently inhibits NF-κB. Spinal cord contusion following laminectomy (T9-10) was performed using a weight drop apparatus (10 g over a 12.5 or 25 mm distance, representing moderate or severe SCI, respectively) in Sprague-Dawley rats. Neural stem cells (NSC) were isolated from subventricular zone (SVZ) and transplanted at the site of injury with or without curcumin treatment. Functional recovery was assessed by BBB score and body weight gain measured up to 6 weeks following SCI. At the conclusion of the study, the mass of soleus muscle was correlated with BBB score and body weight. Stem cell therapy improved recovery from moderate SCI, however, it had a limited effect on recovery after severe SCI. Curcumin stimulated NSC proliferation in vitro, and in combination with stem cell therapy, induced profound recovery from severe SCI as evidenced by improved functional locomotor recovery, increased body weight, and soleus muscle mass. These findings demonstrate that curcumin in conjunction with stem cell therapy synergistically improves recovery from severe SCI. Furthermore, our results indicate that the effect of curcumin extends beyond its known anti-inflammatory properties to the regulation of stem cell proliferation.

Recovery from spinal cord injury using naturally occurring antiinflammatory compound curcumin: laboratory investigation.

OBJECT: Spinal cord injury (SCI) is a debilitating disease. Primary SCI results from direct injury to the spinal cord, whereas secondary injury is a side effect from subsequent edema and ischemia followed by activation of proinflammatory cytokines. These cytokines activate the prosurvival molecule nuclear factor-κB and generate obstacles in spinal cord reinnervation due to gliosis. Curcumin longa is an active compound found in turmeric, which acts as an antiinflammatory agent primarily by inhibiting nuclear factor-κB. Here, the authors study the effect of curcumin on SCI recovery. METHODS: Fourteen female Sprague-Dawley rats underwent T9-10 laminectomy and spinal cord contusion using a weight-drop apparatus. Within 30 minutes after contusion and weekly thereafter, curcumin (60 mg/kg/ml body weight in dimethyl sulfoxide) or dimethyl sulfoxide (1 ml/kg body weight) was administered via percutaneous epidural injection at the injury site. Spinal cord injury recovery was assessed weekly by scoring hindlimb motor function. Animals were killed 6 weeks postcontusion for histopathological analysis of spinal cords and soleus muscle weight evaluation. RESULTS: Curcumin-treated rats had improved motor function compared with controls starting from Week 1. Body weight gain significantly improved, correlating with improved Basso-Beattie-Bresnahan scores. Soleus muscle weight was greater in curcumin-treated rats than controls. Histopathological analysis validated these results with increased neural element mass with less gliosis at the contusion site in curcumin-treated rats than controls. CONCLUSIONS: Epidural administration of curcumin resulted in improved recovery from SCI. This occurred with no adverse effects noted in experimental animals. Therefore, curcumin treatment may translate into a novel therapy for humans with SCI.

High-dose intraarterial verapamil in the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

OBJECT: Because oral calcium channel blockers appear to reduce the severity of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH), interest in their application intraarterially has emerged for cases in which noninvasive means of alleviating vasospasm are unsuccessful. Studies to date have been limited to the administration of low intraarterial doses because of concerns about hemodynamic stability and changes in intracranial pressure. These doses, although effective in cases of milder vasospasm, were inadequate in severe cases. The authors present a series of 10 patients with cerebral vasospasm who underwent 12 procedures in which they received > or = 20 mg of intraarterial verapamil per procedure. METHODS: A retrospective review was undertaken of all patients who underwent endovascular treatment for cerebral vasospasm due to aneurysmal SAH by the senior author between February 2005 and October 2006. Ten patients were identified who had undergone a total of 12 procedures during which > or =20 mg of intraarterial verapamil had been administered. From angiography reports, anesthesia records, and nursing records, we obtained pre- and postverapamil mean arterial blood pressures (MABPs), heart rates, intracranial pressures (ICPs) (when available), and visible changes in the degree of vasospasm. RESULTS: No statistically significant changes in MABP, heart rate, or ICP were observed after administration of > or = 20 mg of intraarterial verapamil, and the degree of improvement in vasospasm was statistically significant based on our grading system. No correlation was found between the change in hemodynamic parameters and the total dose of verapamil. CONCLUSIONS: This study indicates that high-dose intraarterial verapamil may be used to treat cerebral vasospasm without compromising hemodynamic stability or increasing ICP.

Inhibition of x-irradiation-enhanced locomotor recovery after spinal cord injury by hyperbaric oxygen or the antioxidant nitroxide tempol.

OBJECT: Hyperbaric oxygen (HBO), the nitroxide antioxidant tempol, and x-irradiation have been used to promote locomotor recovery in experimental models of spinal cord injury. The authors used x-irradiation of the injury site together with either HBO or tempol to determine whether combined therapy offers greater benefit to rats. METHODS: Contusion injury was produced with a weight-drop device in rats at the T-10 level, and recovery was determined using the 21-point Basso-Beattie-Bresnahan (BBB) locomotor scale. Locomotor function recovered progressively during the 6-week postinjury observation period and was significantly greater after x-irradiation (20 Gy) of the injury site or treatment with tempol (275 mg/kg intraperitoneally) than in untreated rats (final BBB Scores 10.6 [x-irradiation treated] and 9.1 [tempol treated] compared with 6.4 [untreated], p < 0.05). Recovery was not significantly improved by HBO (2 atm for 1 hour [BBB Score 8.2, p > 0.05]). Interestingly, the improved recovery of locomotor function after x-irradiation, in contrast with antiproliferative radiotherapy for neoplasia, was inhibited when used together with either HBO or tempol (BBB Scores 8.2 and 8.3, respectively). The ability of tempol to block enhanced locomotor recovery by x-irradiation was accompanied by prevention of alopecia at the irradiation site. The extent of locomotor recovery following treatment with tempol, HBO, and x-irradiation correlated with measurements of spared spinal cord tissue at the contusion epicenter. CONCLUSIONS: These results suggest that these treatments, when used alone, can activate neuroprotective mechanisms but, in combination, may result in neurotoxicity.

Aeromonas meningitis complicating medicinal leech therapy.

Medicinal leeches have an important and expanding role in medicine, but infection can complicate their use. We describe a unique case of Aeromonas meningitis associated with the use of leech therapy to salvage a skin flap after central nervous system surgery.