RESUMO
Rats receiving a complete spinal cord transection (ST) at a neonatal stage spontaneously can recover significant stepping ability, whereas minimal recovery is attained in rats transected as adults. In addition, neonatally spinal cord transected rats trained to step more readily improve their locomotor ability. We hypothesized that recovery of stepping in rats receiving a complete spinal cord transection at postnatal day 5 (P5) is attributable to changes in the lumbosacral neural circuitry and not to regeneration of axons across the lesion. As expected, stepping performance measured by several kinematics parameters was significantly better in ST (at P5) trained (treadmill stepping for 8 weeks) than age-matched non-trained spinal rats. Anterograde tracing with biotinylated dextran amine showed an absence of labeling of corticospinal or rubrospinal tract axons below the transection. Retrograde tracing with Fast Blue from the spinal cord below the transection showed no labeled neurons in the somatosensory motor cortex of the hindlimb area, red nucleus, spinal vestibular nucleus, and medullary reticular nucleus. Retrograde labeling transsynaptically via injection of pseudorabies virus (Bartha) into the soleus and tibialis anterior muscles showed no labeling in the same brain nuclei. Furthermore, re-transection of the spinal cord at or rostral to the original transection did not affect stepping ability. Combined, these results clearly indicate that there was no regeneration across the lesion after a complete spinal cord transection in neonatal rats and suggest that this is an important model to understand the higher level of locomotor recovery in rats attributable to lumbosacral mechanisms after receiving a complete ST at a neonatal compared to an adult stage.
Assuntos
Coxeadura Animal/fisiopatologia , Regeneração Nervosa/fisiologia , Paralisia/fisiopatologia , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Medula Espinal/fisiopatologia , Fatores Etários , Amidinas , Animais , Animais Recém-Nascidos , Transporte Axonal/fisiologia , Biotina/análogos & derivados , Tronco Encefálico/citologia , Tronco Encefálico/crescimento & desenvolvimento , Dextranos , Modelos Animais de Doenças , Vias Eferentes/crescimento & desenvolvimento , Vias Eferentes/lesões , Vias Eferentes/fisiopatologia , Teste de Esforço , Feminino , Cones de Crescimento/fisiologia , Cones de Crescimento/ultraestrutura , Herpesvirus Suídeo 1 , Coxeadura Animal/etiologia , Coxeadura Animal/terapia , Locomoção/fisiologia , Córtex Motor/citologia , Córtex Motor/crescimento & desenvolvimento , Técnicas de Rastreamento Neuroanatômico , Plasticidade Neuronal/fisiologia , Paralisia/etiologia , Paralisia/terapia , Ratos , Ratos Sprague-Dawley , Medula Espinal/crescimento & desenvolvimento , Medula Espinal/patologia , Traumatismos da Medula Espinal/reabilitação , Coloração e RotulagemRESUMO
It is held that the tail-flick test of pain depends on a spinal reflex because a similar response is observed in spinally transected rats. But when subjects were manually held and a cool heat setting was used, supraspinal systems facilitated the response (Experiment 1). This effect did not depend on the rate at which the tail was heated (Experiment 2) but rather on the co-occurrence of visual, auditory, and tactile cues that predict impending pain (Experiments 3 and 4). Subjects rapidly learned to exhibit a tail movement during these co-occurring cues, and this avoidance response was instrumental in nature (Experiment 5). Optimal learning was observed when the visual signal was presented 8-12 s before a heat-elicited response is normally observed (Experiment 6), and a low dose of morphine inhibited the performance of the instrumental response (Experiment 7).