RESUMO
Dorsal root injury is a situation not expected to be followed by a strong regenerative growth, or growth of the injured axon into the central nervous system of the spinal cord, if the central axon of the dorsal root is injured but of strong regeneration if subjected to injury to the peripherally projecting axons. The clinical consequence of axonal injury is loss of sensation and may also lead to neuropathic pain. In this study, we have used in situ hybridization to examine the distribution of mRNAs for the neural guidance molecules semaphorin 3A (SEMA3A), semaphorin 3F (SEMA3F), and semaphorin 4F (SEMA4F), their receptors neuropilin 1 (NP1) and neuropilin 2 (NP2) but also for the neuropilin ligand vascular endothelial growth factor (VEGF) and Tenascin J1, an extracellular matrix molecule involved in axonal guidance, in rat dorsal root ganglia (DRG) after a unilateral dorsal rhizotomy (DRT) or sciatic nerve transcetion (SNT). The studied survival times were 1-365 days. The different forms of mRNAs were unevenly distributed between the different size classes of sensory nerve cells. The results show that mRNA for SEMA3A was diminished after trauma to the sensory nerve roots in rats. The SEMA3A receptor NP1, and SEMA3F receptor NP2, was significantly upregulated in the DRG neurons after DRT and SNT. SEMA4F was upregulated after a SNT. The expression of mRNA for VEGF in DRG neurons after DRT showed a significant upregulation that was high even a year after the injuries. These data suggest a role for the semaphorins, neuropilins, VEGF, and J1 in the reactions after dorsal root lesions.
Assuntos
Política de Saúde , Papel do Médico , Política de Saúde/tendências , Humanos , Liderança , SuéciaRESUMO
Spinal cord injury is frequently associated with local tissue hypoxia. As neuronal cells are susceptible to damage caused by low oxygen levels, hypoxia-induced activation of tissue-protective factors could represent an endogenous mechanism for neuron survival following injury. We studied in vivo, in a rat model of intraspinal axotomy of motoneurons, the cell- and time-dependent regulation of the hypoxia-inducible transcription factors (HIFs), HIF1alpha and HIF2alpha, as well as one of their target genes, vascular endothelial growth factor (VEGF). VEGF is a potent hypoxia-regulated angiogenic growth factor with recently discovered neuroprotective and neurotrophic activities. While neither HIF1alpha, HIF2alpha, nor VEGF mRNA were detected in noninjured motoneurons, we found a strong induction of HIF1alpha, but not HIF2alpha mRNA in axotomized motoneurons. HIF1alpha expression peaked at about 7 days after injury. Moreover, we found increased VEGF mRNA and protein expression around and within the scar but also within motoneurons, peaking around 3 days after axotomy. In addition, increased survival of cultured motoneurons after treatment with VEGF could also be shown. We conclude that axotomized motoneurons in this model respond to injury by specific induction of HIF1alpha and VEGF expression that may provide an endogenous mechanism with the potential to promote motoneuron survival after injury.