BackgroundAfter facial nerve injury and surgical repair in rats, recovery of vibrissal whisking is associated with a high proportion of mono‐innervated neuro‐muscular junctions (NMJs). Our earlier work with Sprague Dawley (SD)/Royal College of Surgeons (RCS) rats, which are blind and spontaneously restore NMJ‐monoinnervation and whisking, showed correlations between functional recovery and increase of fibroblast growth factor‐2 (FGF2) and brain‐derived neurotrophic factor (BDNF) in denervated vibrissal muscles.MethodsWe used normally sighted rats (Wistar), in which NMJ‐polyinnervation is highly correlated with poor whisking recovery, and injected the vibrissal muscle levator labii superioris (LLS) with combinations of BDNF, anti‐BDNF, and FGF2 at different postoperative periods after facial nerve injury.ResultsRats receiving anti‐BDNF+FGF2 showed low NMJ‐polyinnervation and best recovery of whisking amplitude.ConclusionsRestoration of target reinnervation after peripheral nerve injury requires a complex mixture of trophic factors with a specific time course of availability for each of them.
Transection and re-anastomosis of the purely motor facial nerve leads to poor functional recovery. However, we have recently shown in rat that manual stimulation (MS) of denervated vibrissal muscles reduces the number of polyinnervated motor endplates and promotes full recovery of whisking. Here, we examined whether MS of denervated rat forearm muscles would also improve recovery following transection and suture of the mixed (sensory and motor) median nerve (median-median anastomosis, MMA). Following MMA of the right median nerve, animals received no postoperative treatment, daily MS of the forearm muscles or handling only. An almost identical level of functional recovery, measured by the force of grip in grams, was reached in all animals by the sixth postoperative week and maintained till 3 months following surgery regardless of the postoperative treatment. Also, we found no differences among the groups in the degree of axonal sprouting, the extent of motor endplate polyinnervation and in the soma size of regenerated motoneurons. Taken together, we show that while MS is beneficial following motor nerve injury, combined strategies will be required for functional recovery following mixed nerve injury.
The main stem cell niche for neurogenesis in the adult mammalian brain is the subventricular zone (SVZ) that extends along the cerebral lateral ventricles. We aimed at characterizing the initial molecular responses of the macaque monkey SVZ to transient, global cerebral ischemia. We microdissected tissue lining the anterior horn of the lateral ventricle (SVZa) from 7 day post-ischemic and sham-operated monkeys. Transcriptomics shows that in ischemic SVZa, 541 genes were upregulated and 488 genes were down-regulated. The transcription data encompassing the upregulated genes revealed a profile typical for quiescent stem cells and astrocytes. In the primate brain the SVZ is morphologically subdivided in distinct and separate ependymal and subependymal regions. The subependymal contains predominantly neural stem cells (NSC) and differentiated progenitors. To determine in which SVZa region ischemia had evoked transcriptional upregulation, sections through control and ischemic SVZa were analyzed by high-throughput in situ hybridization for a total of 150 upregulated genes shown in the www.monkey-niche.org image database. The majority of the differentially expressed genes mapped to the subependymal layers on the striatal or callosal aspect of the SVZa. Moreover, a substantial number of upregulated genes was expressed in the ependymal layer, implicating a contribution of the ependyma to stem cell biology. The transcriptome analysis yielded several novel gene markers for primate SVZa including the apelin receptor that is strongly expressed in the primate SVZa niche upon ischemic insult.
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