cPKCγ Inhibits Caspase-9-Initiated Neuronal Apoptosis in an Ischemia Reperfusion Model In Vitro Through p38 MAPK-p90RSK-Bad Pathway.

Strokes are one of the leading causes of death and disability in the world. Previously we have found that conventional protein kinase Cγ (cPKCγ) plays neuroprotective role in ischemic strokes. Further, we found that cPKCγ knockdown increased the level of cleaved (cl)-Caspase-3. However, the precise mechanisms underlying cPKCγ-mediated neuronal death remain unclear. To this end, a model incorporating 1 h oxygen-glucose deprivation/24 h reoxygenation (1 h OGD/24 h R) was established in cortical neurons. We found that cPKCγ knockdown remarkably increased neuronal death after OGD. We also found that cPKCγ knockdown increased the level of cl-Caspase-3 through the upstream initiators Capsases-9 (not Caspase-8/12) in OGD-treated neurons. Overexpression of cPKCγ could decrease neuronal death and cl-Caspase-3 and -9 levels. Moreover, cPKCγ knockdown further reduced the phosphorylation levels of p38 MAPK, p90RSK, and Bad. In addition, the protein levels of Bcl-2 and Bcl-xl were decreased after cPKCγ knockdown, whereas that of Bax was increased. In conclusion, our results suggest that cPKCγ partly alleviates ischemic injury through activating the p38 MAPK-p90RSK-Bad pathway and inhibiting Caspase-9 initiated apoptosis. This may have potential as a therapeutic target for ischemic stroke.

Early Aerobic Exercise Promotes Neurological Function Recovery of Rats after Cerebral Ischemia/Reperfusion by Upregulating the Expression of Heat Shock Protein A5.

OBJECTIVE: The neuroprotective function of heat shock protein A5 (HSPA5) in ischemic stroke has been confirmed. This study aimed to investigate the effects of early aerobic exercise on neurological function recovery from cerebral ischemia/reperfusion and to determine whether these effects are associated with the expression level of HSPA5 in the ischemic penumbra. METHODS: A total of 72 male Sprague-Dawley rats were randomly assigned to the ischemia and exercise group [middle cerebral artery occlusion (MCAO)-Ex, n=18], ischemia and sedentary group (MCAO-St, n=18), sham-surgery and exercise group (Sham-Ex, n=18), or sham-surgery and sedentary group (Sham-St, n=18). The MCAO-Ex and MCAO-St groups were subjected to MCAO for 60 min, whereas the Sham-Ex and Sham-St groups were subjected to an identical operation without MCAO. Rats in the MCAO-Ex and Sham-Ex groups then ran on a treadmill for 30 min once a day for 5 consecutive days. After reperfusion, the motor function of the rats was scored by the Bederson neurological function test, balance beam test, and screen test. Nissl staining was conducted to assess morphological and structural change of nerve cells in the ischemic penumbra. The reverse transcription-quantitative polymerase chain reaction was applied to detect the mRNA expression of HSPA5. Western blot analysis was conducted to determine the protein expression of HSPA5. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was carried out in the ischemic penumbra after MCAO. RESULTS: Rats receiving early treadmill exercise had lower Bederson neurological function, balance beam, and screen test scores on the 3rd, 7th, and 14th days after MCAO; in addition, more neurons survived in the ischemic penumbra after MCAO, and higher mRNA and protein expression of HSPA5 and fewer TUNEL-positive stained cells were observed. CONCLUSION: Our study demonstrated that early aerobic exercise can improve neurological function recovery after ischemia/reperfusion. Furthermore, the increased level of HSPA5 in the ischemic penumbra might be one of the mechanisms of enhanced neurological function recovery.

[Effects of heat shock protein A5 induced autophagy on cerebral ischemia/reperfusion injury in mice].

OBJECTIVE: To determine the role of heat shock protein A5 (HSPA5) induced autophagy on cerebral ischemia/reperfusion in-jury in mice. METHODS: Thirty-six BALB/c mice were randomly divided into sham group, ischcmia/reperfusion (I/R) group, vehicle + I/R group, 3-Methyladenine(3-MA) + I/R group, scramble siRNA group and HSPA5 siRNA + I/R group(n=6). In sham group, the operation was only performed, did not insert line switch. Focal cerebral ischemia was performed using the method of middle cerebral artery occlusion (MCAO) for 60 min and 24 h reperfusion. In vehicle + I/R group and 3-MA + I/R group, 2µl 0.9% NaCl or 3-MA(30 mg/ml) was admin-istered by intracerebroventricular injection 30 min before MCAO; In scramble siRNA + I/R group and HSPA5 siRNA + I/R group, 5µl scram-ble siRNA or HSPA5 siRNA(2µg/µl) was administered by intracerebroventricular injection 24 h before MCAO. Autophagosome in neuron, the expression of microtubule-associated protein light chain 3 (LC3)-Ⅱ/LC3-I in ischemic cortex, the degree of cerebral ischemic injury and neu-rological function score were detected. RESULTS: Initial electron microscopy showed that neuronal morphology appeared to be normal in the sham group. At 24 h after I/R, cell shrinkage, loss of cellular organelles and formation of autophagosomes were observed in the ischemic cerebral cortex of I/R group. In addition, autophagosomes were less frequently observed than that in I/R group. The expressions of LC3-Ⅱ/LC3-I and Beclin-1 protein were increased significantly in I/R group compared with that in sham group(P < 0.05). Compare with I/R group, the LC3-Ⅱ/LC3-I protein levels induced by I/R in 3-MA + I/R group or HSPA5 siRNA + I/R group was decreased effectively (P < 0.05). In addi-tion, the cerebral ischemic injury and neurological symptoms after I/R in 3-MA + I/R group or HSPA5 siRNA + I/R group were exacerbated significantly (P < 0.05). CONCLUSIONS: These results suggest that HSPA5 induced autophagy may play a protective role in focal I/R damage in mice.

Design of multi-functional forceps / 局解手术学杂志

Objective To introduce the design of a multi-functional medical forceps which containing the functions of cutting , easily conversion between tooth forceps and toothless forceps .Methods To design a multi-functional medical forceps ,including forceps arm ,blade groove,blade retaining plate,first magnet,forceps rotating parts,fixed plate groove,second magnets,forceps groove,slider,metal sleeve and two protection slot,which containing the functions of cutting ,easily conversion between tooth forceps and toothless forceps ,and so on.Results The multifunctional medical forceps can prevent unstable tissue clamp and achieve the conversion between tooth forceps and toothless forceps . Moreover,the cutting function can be achieved when the tissue is to be cut .Conclusion The multi-functional medical forceps can theoreti-cally solve the problems caused by the traditional forceps in the exchange of instruments , and it can save the time of changing medical ma-chinery so as to achieving the purpose of reducing the operation time and improving the operation efficiency .

[Activation of periphery group III metabotropic glutamate receptors inhibits formalin-induced activation of spinal p38-MAPK in rats].

AIM: To explore the effects of periphery injection of L-SOP on the activation of p38MAPK in spinal cord in formalin pain model in rats. METHODS: Fourty-eight male Wistar rats were divided randomly into four groups (n=12): NS group and three different dose of L-SOP groups. For each group, 6 rats used to observe flinching and licking time every as nociception behavior 3 minutes in 1 hour after formalin injected and the other 6 rats used to observe the activation of p38(P-p38) by Western blotting. RESULTS: All the three different groups of L-SOP could inhibit nociception behavior in the tonic phase,and 250 nmoVl/L and 500 nmol/L groups could suppress not only in the tonic phase but also in the acute phase. 250 nmol/L and 500 nmol/L groups could reduce activated or phosphorylated p38MAPK in spinal cord. CONCLUSION: Periphery injection of L-SOP can reduce nociceptive behavior and phosphorylated p38MAPK in the spinal cord in formalin-induced hyperalgia, it is suggested that there is functional expression of mGluRs III in the periphery and is involved in the processing of peripheral noxious informations.