Neuroscience letters
-
Neuroscience letters · Nov 2008
Intranasally delivered bFGF enhances neurogenesis in adult rats following cerebral ischemia.
Basic fibroblast growth factor (bFGF) is a very important mitogenic factor with proved neurogenesis effects in the central nervous system. Intranasal administration can bypass blood-brain barrier and deliver drugs into the brain directly. We investigated whether intranasal administration of bFGF at later time points after ischemia could promote adult neurogenesis and improve neurologic functions. ⋯ Compared with the control animals, intranasal administration of bFGF improved behavioral recovery without affecting infarct size, and enhanced proliferation of progenitor cells in the subventricular zone and the subgranular zone of the dentate gyrus (DG). Furthermore, the new proliferated cells could differentiate into neurons (BrdU+NeuN+ cells) in the striatum and DG at 28 days after MCAO. Intranasal administration of bFGF offers a non-invasive alternative for the treatment of stroke.
-
Neuroscience letters · Nov 2008
Pressure pain precedes development of type 2 disease in Zucker rat model of diabetes.
Decreased hind limb pressure pain threshold (PPT) is an early indicator of insulinopenia and neuropathy developing in STZ-rat models of type 1 diabetes and pre-diabetes. To test if pain on pressure is also a hallmark of compensated insulin resistance and type 2 diabetes in this work we measured PPT of Zucker lean (ZL), Zucker fatty (ZF) and Zucker fatty diabetic rats (ZDF; 8 animals per group). Using clinically accepted cut-off values for diagnosis of human diabetes and pre-diabetes, at 6th week of age (the study entry), all animals maintained random blood glucose within a normal range (< 7.9 mM). ⋯ With no detectable relation to blood glucose levels or changes throughout the study, lean, ZF and ZDF rats maintained respectively highest, intermediate and lowest PPT levels (83+/-1, 70+/-1 and 59+/-1 g; mean values for all tests per group). Thus in Zucker rat model, type 2 diabetes-associated impairment of nerve function precedes the development of hyperglycemia. Furthermore, since normoglycemic, but displaying decreased PPT, ZF rats were strongly hyperinsulinemic (plasma insulin concentration 30+/-4 ng/ml vs. 2.4+/-0.3 ng/ml in lean rats) these data suggest that hyperinsulinemia compensating for glucose metabolism might not restore compromised nerve function.
-
Neuroscience letters · Nov 2008
Differential effects of spinally applied glycine transporter inhibitors on nociception in a rat model of neuropathic pain.
Changes in glycinergic neurotransmission in the spinal cord dorsal horn are critically involved in the development of pathological pain. Since the concentration of glycine in the synaptic cleft is controlled by specialized proteins, the glycine transporters GlyT1 and GlyT2, manipulation of this system might have significant effects on nociception. In the present study, we investigated the effects of the spinally applied glycine transporter inhibitors ALX 5407 (GlyT1) and ALX 1393 (GlyT2) on nociceptive behavior in the chronic constriction injury model of neuropathic pain in male Wistar rats. ⋯ However, in the same dose, ALX 1393 caused remarkable side effects such as respiratory depression and motor deficits in three animals. Our findings indicate that inhibition of glycine transporters is capable of evoking significant effects on nociceptive behavior in neuropathic pain. Whether glycine transporter inhibitors have the capability to gain clinical relevance as analgesic compounds on the long run has to be elucidated in further investigations.
-
Neuroscience letters · Nov 2008
Up-regulation of tumor necrosis factor-alpha in spinal cord contributes to vincristine-induced mechanical allodynia in mice.
Chronic treatment with vincristine (VCR) causes mechanical allodynia as an adverse effect. We previously reported that peripheral macrophage-derived interleukin-6 played a critical role in VCR-induced allodynia. However, the involvement of glial cell activation and central sensitization in VCR-induced allodynia is still unclear. ⋯ The immunoreactivity of TNF-alpha was co-localized in some of the activated microglia and astrocytes. In behavioral analysis, a neutralizing antibody of TNF-alpha, which was injected intrathecally on days 0, 3, and 6, significantly attenuated VCR-induced mechanical allodynia on days 4 and 7. These results suggest that VCR treatments elicited the activation of glial cells in spinal cord, and up-regulated TNF-alpha in these cells may play an important role in VCR-induced mechanical allodynia.
-
Neuroscience letters · Nov 2008
The vestibular system is integral in regulating plastic alterations in the pressor response to free drop mediated by the nonvestibular system.
Microgravity resulting from free drop elicits a pressor response that involves both vestibular and nonvestibular pathways. In rats reared under a 3G environment for 2 weeks, plastic alterations in both vestibular- and nonvestibular-mediated responses are induced; specifically, the pressor responses involving both pathways are reduced [C. Abe, K. ⋯ To examine this topic, the pressor response to free drop was compared between rats with and without vestibular lesion (VL) reared under 1G or 3G environments. The pressor response to free drop was 34+/-3mmHg in vestibular intact rats reared under 1G, and was significantly attenuated in rats reared under a 3G environment for 2 weeks (13+/-3mmHg); however, the pressor response was similar between VL-1G (18+/-3mmHg) and VL-3G (19+/-3mmHg) rats. Therefore, the 3G environment induced plastic alterations in the pressor response to free drop mediated by both the vestibular and nonvestibular systems, and the vestibular system is indispensable for induction of the plastic alteration of the nonvestibular-meidated pressor response to free drop.