Effects of dantrolene on apoptosis and immunohistochemical expression of NeuN in the spinal cord after traumatic injury in rats

Abstract

Dantrolene has been shown to be neuroprotective by reducing neuronal apoptosis after brain injury in several animal models of neurological disorders. In this study, we investigated the effects of dantrolene on experimental spinal cord injury (SCI). Forty-six male Wistar rats were laminectomized at T13 and divided in six groups: GI (n = 7) underwent SCI with placebo and was euthanized after 32 h; GII (n = 7) underwent laminectomy alone with placebo and was euthanized after 32 h; GIII (n = 8) underwent SCI with dantrolene and was euthanized after 32 h; GIV (n = 8) underwent SCI with placebo and was euthanized after 8 days; GV (n = 8) underwent laminectomy alone with placebo and was euthanized after 8 days; and GVI (n = 8) underwent SCI with dantrolene and was euthanized after 8 days. A compressive trauma was performed to induce SCI. After euthanasia, the spinal cord was evaluated using light microscopy, TUNEL staining and immunochemistry with anti-Caspase-3 and anti-NeuN. Animals treated with dantrolene showed a smaller number of TUNEL-positive and caspase-3-positive cells and a larger number of NeuN-positive neurons, both at 32 h and 8 days (P ≤ 0.05). These results showed that dantrolene protects spinal cord tissue after traumatic SCI by decreasing apoptotic cell death.

Dantrolene e células-tronco mesenquimais promovem melhora funcional em ratos Wistar com trauma espinhal agudo

“…Entretanto, esses animais apresentaram maior preservação neuronal (neurônios NeuN-positivos) e menor número de células apoptóticas (caspase-3-positivas), em comparação aos animais que receberam apenas placebo (Torres et al 2010a). Por isso, aventou-se a necessidade de avaliação clínica por tempo prolongado para observar efeitos clinicamente positivos, devido à gravidade do trauma.…”

“…Cristália Produtos Químicos Farmacêuticos Ltda. Itapira, SP, Brasil) ou volume equivalente de seu placebo (água estéril para injeção), ambos pela via intraperitoneal, conforme Torres et al (2010a). Sete dias após a cirurgia, os animais foram tratados com 200µL de PBS contendo 1x10 6 de CTM ou volume equivalente de seu placebo (200 µL de PBS), aplicados pela veia lateral da cauda.…”

“…Seus efeitos neuroprotetores em modelos de trauma espinhal ex vivo, in vivo e in vitro já foram demonstrados (Thorell et al 2002, Kocogullari et al 2008, Aslan et al 2009). Recentemente, nosso grupo de pesquisa demonstrou, pela primeira vez, o potencial efeito neuroprotetor do dantrolene por inibição de apoptose neuronal em modelo in vivo de trauma espinhal agudo (TEA) (Torres et al 2010a).…”

Neuroprotective effect of ketamine on acute spinal cord injury in rats

“…Neuronal apoptosis, which is a secondary injury after ASCI, is of great interest (Torres et al, 2010). In the terminal stages of injury, hematomas formed due to mechanical compression, reduction of local blood flow, release of blood components, an increase in various cytotoxic substances, and the generation of oxygen free radicals, ultimately initiates apoptosis (Emery et al, 1998).…”

ω-conotoxin MVIIA intralesional injection in spinal cord injury in rats

“…Using the spiny process of T13 as a landmark, laminectomy of T12 was performed with a pneumatic drill and the lamina was carefully removed to expose the spinal cord. Extradural compression of the spinal cord at the vertebral level of T12 was achieved as previously described (TORRES et al, 2010;OLIVEIRA et al, 2014) for five minutes, using a weigh of 40.5g cm…”