ABSTRACT
Axon regeneration after cerebral ischemia in mammals is inadequate to restore function, illustrating the need to design better strategies for improving outcomes. Improvement of axon regeneration has been achieved through fastigial nucleus electrostimulation (FNS) in animal researches. However, the mechanisms underlying this neuroprotection remain poorly understood. Increasing the levels of the second messenger cyclic AMP (cAMP) enhances axon regeneration, making it an excellent candidate molecule that has therapeutic potential. In the present study, we examined the expression of cAMP signaling in ischemic brain tissues following focal cerebral ischemia. Adult rats were subjected to ischemia induced by middle cerebral artery occlusion (MCAO). A dipolar electrode was placed into the cerebellum to stimulate the cerebellar fastigial nucleus for 1 h after ischemia. Neurological deficits and the expressions of cAMP, PKA (protein kinase A) and ROCK (Rho-kinase) were determined. Axonal regeneration was measured by upregulation of growth-associated protein 43 (GAP43). The data indicated that FNS significantly enhanced axonal regeneration and motor function recovery after cerebral ischemia. FNS also significantly increased cAMP and PKA levels after ischemic brain injury. All the beneficial effects of FNS were blocked by Rp-cAMP, an antagonist of PKA. Our research suggested that the axonal regeneration conferred by FNS was likely achieved via the regulation of cAMP/PKA pathway.
Subject(s)
Cerebellar Nuclei/physiology , Cyclic AMP-Dependent Protein Kinases/metabolism , Cyclic AMP/metabolism , Electric Stimulation Therapy , Infarction, Middle Cerebral Artery/therapy , Nerve Regeneration , Signal Transduction , Animals , Cerebellar Nuclei/drug effects , Cyclic AMP/analogs & derivatives , Cyclic AMP/pharmacology , GAP-43 Protein/metabolism , Infarction, Middle Cerebral Artery/metabolism , Infarction, Middle Cerebral Artery/pathology , Male , Nerve Regeneration/drug effects , Rats , Recovery of Function/drug effects , Thionucleotides/pharmacology , Up-Regulation , rho-Associated Kinases/biosynthesisABSTRACT
OBJECTIVE: To investigate the effects of Gypsum Fibrosum and Gypsum Fibrosum Preparatum in promoting granulation. METHODS: The wounds of muscle layer were produced in rats by using surgical operation. Two round wounds, with diameter about 1.5 cm, were cut at the depilatory area of two sides of the back of each rat, with an interval of 2 cm, deep to muscle layer, and the thickness of the knife wound of muscle layer was about 0.15 cm. Forty SD rats with the wounds were randomly divided into 4 groups: untreated group, beifuji-treated group, Gypsum Fibrosum-treated group and Gypsum Fibrosum Preparatum-treated group, with 10 rats in each group. Then the wounds were sprinkled with powders of Gypsum Fibrosum and Gypsum Fibrosum Preparatum, or sprayed with beifuji solution, respectively. The healing state of granulation tissues of the wounds was observed at the eighth and fourteenth day respectively. RESULTS: The number of fibroblasts, the number of capillary tubes and the area of capillary tubes in granulation tissue of wounds in the Gypsum Fibrosum Preparatum-treated group were significantly higher than those in the untreated group and Gypsum Fibrosum-treated group (P<0.01). There were no statistical differences between the Gypsum Fibrosum Preparatum-treated group and the beifuji-treated group. However, Gypsum Fibrosum-treated group showed no obvious differences compared to the untreated group (P>0.05). CONCLUSIONS: Gypsum Fibrosum Preparatum can accelerate the formation of collagenoblast and micrangium in wounds, and the proliferation of granulation tissues, thus promoting the skin wounds to healing. The effect of Gypsum Fibrosum is changed after being calcined, and Gypsum Fibrosum Preparatum has obvious effect in promoting granulation.