Brain research
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Cerebral ischemia/reperfusion injury can result in neuronal death, which further results in brain damage and can even lead to death. Although recent studies showed that rosmarinic acid (RA) exerts neuroprotective effects and attenuates ischemia-induced brain injury and neuronal cell death, little is known about the precise mechanisms that occur during cerebral ischemia/reperfusion (I/R). Therefore, the aim of this study was to examine the underlying mechanism of the neuroprotective effects of RA against ischemic brain injury induced by cerebral I/R. ⋯ Additionally, RA significantly protected neurons in the hippocampal CA1 region against cerebral I/R-induced damage. Furthermore, RA increased the phosphorylation of Akt1, downregulated the phosphorylation of JNK3 and reduced the expression of cleaved caspase-3. Finally, the Akt inhibitor LY294002 reversed all the protective effects of RA, indicating that RA protects neurons in the hippocampal CA1 region from ischemic damage through the Akt/JNK3/caspase-3 signaling pathway.
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The pituitary adenylyl cyclase-activating polypeptide (PACAP) and its G protein-coupled receptors, PAC1, VPAC1 and VPAC2 form a system involved in a variety of biological processes. Although some sympathetic stimulatory effects of this system have been reported, its central cardiovascular regulatory properties are poorly characterized. ⋯ In vivo, this pathway converges onto transient reduction in heart rate of conscious rats. Therefore we demonstrate a VPAC1-dependent mechanism in the central parasympathetic regulation of the heart rate, adding to the complexity of PACAP-mediated cardiovascular modulation.
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Increasing evidence demonstrates an association between diabetes and hippocampal neuron damage. This study aimed to determine the effects of troxerutin on cognitive deficits and glutamate cysteine ligase subunits (GCLM and GCLC) in the hippocampus of streptozotocin-induced type 1 diabetes mellitus (T1DM) rats. At 12weeks after streptozotocin injection, T1DM rats were randomly divided into 4 groups (n=15 each group) to receive no treatment (T1DM), saline (T1DM+saline), alpha-lipoic acid (T1DM+alpha-lipoic acid), and troxerutin (T1DM+troxerutin), respectively, for 6weeks. ⋯ Significantly increased GCLM and GCLC mRNA levels, GCLC protein amounts, SOD activity, and GSH levels, and reduced MDA amounts were observed in T1DM+alpha-lipoic acid and T1DM+troxerutin groups. In T1DM and T1DM+saline groups, H&E staining showed less pyramidal cells in the hippocampus, with disorganized layers, karyopyknosis, decreased endochylema, and cavitation, effects relieved in T1DM+alpha-lipoic acid and T1DM+troxerutin groups. Troxerutin alleviates oxidative stress and promotes learning in streptozotocin-induced T1DM rats, a process involving GCLC expression.
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The amide-type local anesthetic (LA) lidocaine activates transient receptor potential (TRP) ankyrin-1 (TRPA1) channels to facilitate spontaneous l-glutamate release onto spinal substantia gelatinosa (SG) neurons, which play a crucial role in regulating nociceptive transmission. In contrast, the ester-type LA procaine reduces the spontaneous release of l-glutamate in SG neurons. In order to determine whether TRPA1 activation by LAs is specific to amide-types, we examined the actions of tetracaine, another ester-type LA, and other amide-type LAs on glutamatergic spontaneous excitatory transmission in SG neurons by focusing on TRP activation. ⋯ In conclusion, tetracaine facilitated spontaneous l-glutamate release from nerve terminals by activating TRPA1 channels in the SG, resulting in an increase in the excitability of SG neurons. TRPA1 activation was not specific to amide-type or ester-type LAs. The facilitatory action of LAs may be involved in pain occurring after recovery from spinal anesthesia.
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The use of forced-swim, rat-validated cognition tests in mouse models of traumatic brain injury (TBI) raises methodological concerns; such models are vulnerable to a number of confounding factors including impaired motor function and stress-induced non-compliance (failure to swim). This study evaluated the ability of a Radial Water Tread (RWT) maze, designed specifically for mice, that requires no swimming to distinguish mice with controlled cortical impact (CCI) induced TBI and Sham controls. ⋯ The Radial Water Tread maze capitalizes on the natural tendency of mice to avoid open areas in favor of hugging the edges of an apparatus (thigmotaxis), and replaces a forced-swim model with water shallow enough that the animal is not required to swim, but aversive enough to motivate escape. Our findings indicate the RWT task is a sensitive species-appropriate behavioral test for evaluating spatial memory impairment in a mouse model of TBI.