Nitin Bansal

Caffeic acid phenethyl ester (CAPE) prevents development of STZ-ICV induced dementia in rats

Background: Chronic oxidative stress and inflammation severely affect the normal physiology of neurons and lead to neurodegenerative disorders such as Alzheimers disease (AD). Polyphenols proved a boon in the prevention of dementia due to their antioxidant and neuroprotective potential. Caffeic acid phenethyl ester (CAPE) is a natural polyphenolic compound attributed with antioxidant, immunomodulatory, and neuroprotective properties. Objective: The present study investigates the effect of CAPE on experimental dementia in rats. Methods: Intracerebroventricle (ICV) injection of streptozotocin (STZ; 3 mg/kg) was given to Wistar rats (200 g, either sex) on days 1 and 3 to induce dementia of AD type. CAPE (3 and 6 mg/kg, i.p.) was administered to separate groups of rats for 28 successive days daily. Morris water maze and elevated plus maze served as exteroceptive behavioral models to measure the memory of the rats. Results: The present study illustrated that CAPE treatment for 28 consecutive days arrested the development of cognitive deficits in STZ-ICV-treated rats, that is, a significant (P < 0.05) reduction in the mean escape latency during acquisition trial and increased (P < 0.05) time spent in target quadrant during retrieval trial in Morris water maze test and reduction (P < 0.05) in transfer latency in elevated plus maze test. Furthermore, both the doses of CAPE when administered to rats that were previously treated with STZ-ICV prevented the rise of brain thiobarbituric acid reactive substance as well as TNF-α and simultaneously enhanced the GSH content. Conclusion: CAPE administration ameliorated STZ-ICV-induced dementia through the attenuation of oxidative stress and inflammation. Abbreviation used: AD: Alzheimers disease, ANOVA: Analysis of Variance, aCSF: Artificial cerebrospinal fluid, CAPE: Caffeic acid phenethylester, EPM: Elevated plus maze, ELT: Escape latency time, GSH: Reduced glutathione, IL: Interleukin, ICV: Intracerebroventricular, MDA: Malondialdehyde, MEL: Mean escape latency, MWM: Morris water maze, NFTs: Neurofibrillary tangles, RNS: Reactive nitrogen species, ROS: Reactive oxygen species, SEM: Standard error of mean, STZ: Streptozotocin, TBARS: Thiobarbituric reactive substances, TSTQ: Time spent in target quadrant, TL: Transfer latency, TNF-α: Tumor necrosis factor alpha.

Ellagic Acid Administration Negated the Development of Streptozotocin-Induced Memory Deficit in Rats

Rampant production of pro-oxidants and inadequate antioxidant availability in brain exert oxidative stress, which in synergism with impaired glucose metabolism and inflammation leads to neurodegeneration and cognitive deficits. Ellagic acid (EGA) is a phenolic compound present in various fruits and is reported to possess robust antioxidant and anti-inflammatory properties. The present study investigated the effect of EGA administration on streptozotocin (STZ) induced dementia in rats. Bilateral intracerebroventricle (ICV) injection of STZ (3 mg/kg) was given to Wistar rats (200 g) on day 1 and 3. EGA (17.5 and 35 mg/kg) was administered orally to rats for 28 days daily. The spatial memory of rats was quantified by using Morris water maze and elevated plus maze. Brain TBARS, GSH and TNF-α were also measured. Administration of EGA prevented the induction of STZ-ICV triggered cognitive deficits as evident by a significant (p<0.05) reduction in mean escape latency during acquisition trial and increased (p<0.05) time spent in target quadrant during retrieval trial in Morris water maze test, and reduction (p<0.05) in transfer latency in elevated plus maze test. Furthermore, both the doses of EGA attenuated STZ-ICV induced rise in brain TBARS as well as TNF-α and simultaneously enhanced the GSH content. Thus, EGA ameliorated STZ-induced dementia by probably restoring the balance between cellular pro-oxidants and anti-oxidants in brain of rats.

Caffeic acid phenethyl ester rescued streptozotocin-induced memory loss through PI3-kinase dependent pathway

The present study was undertaken to elucidate the role of PI3-kinase signaling in memory enhancing potential of caffeic acid phenethyl ester (CAPE) against cognitive defects in rats after centrally administered streptozotocin as a model of Alzheimers disease. The Morris water maze and elevated plus maze paradigms showed profound loss of memory in adult Wistar rats (180-200 g) injected with streptozotocin (3 mg/kg) bilaterally (STZ-ICV) on day 1 and 3. Intraperitoneal administration of CAPE (6 mg/kg, i.p., 28 days) attenuated STZ-ICV triggered memory loss in rats. Treatment with PI3-kinase inhibitor (wortmannin, 5 μg/rat, ICV) or NOS blocker (L-NAME, 20 mg/kg, i.p., 28 days) interfered with memory restorative function of CAPE in STZ treated rats. In biochemical analysis markers of oxidative stress (TBARS, GSH, SOD, CAT), nitrite, AChE, TNF-α, eNOS and NFκB were measured in brain of rats on day 28. Interestingly, L-Arginine (100 mg/kg, i.p., 28 days) group exhibited moderate (p > 0.05) decline in memory functions. The brain oxidative stress, TNF-α, AChE activity and NFκB levels were elevated, and eNOS level was lowered by STZ-ICV treatment. Administration of CAPE lowered oxidative stress, AChE, nitrite and TNF-α levels in brain of rats. The eNOS level was enhanced and NFκB level was decreased by CAPE in STZ treated rats. Wortmannin injection elevated the brain oxidative stress, AChE activity and TNF-α levels, and decreased the nitrite, eNOS and NFκB level. Rise of brain oxidative stress parameters, AChE activity, TNF-α, eNOS and NFκB levels, and decline in brain nitrite content was observed in L-NAME treated group. L-Arginine administration showed modest effects (p > 0.05) on oxidative stress parameters. Brain nitrite content was enhanced although eNOS, NFκB levels, and AChE activity was decimated by L-Arginine treatment. It can be concluded that PI3-kinase mediated nitric oxide facilitation is an essential feature of CAPE action in STZ-ICV treated rats.

Nerve conduction studies in the upper limb in the malwa region-normative data.

OBJECTIVE To establish the normal electrophysiological data for the median and the ulnar nerves in normal healthy adults in the Malwa region of Punjab, India. METHODS Nerve conduction studies were performed prospectively in the upper limbs of 100 carefully screened, healthy individuals of either sex, who were between the ages of 20 and 60 years, by using a standardized technique. RESULTS Motor studies: The median distal latency (DL) in men was 3.4 (0.2) ms, the amplitude (CMAPA) was 10.80 (2.8) mV, the conduction velocity (MNCV) was 55.6 (2.5) m/s and the F-wave (min latency) was 27.57±2.54(21.5-34.2). In the ulnar nerve , the motor DL was 2.34 (0.25) ms, the amplitude (CMAPA) was 9.8(2.6) mV, MNCV was 63.4 (3.0) m/s and the F-Wave(min latency) was 26.29±2.12(21.6-34.7). In the sensory studies, the median nerve DL was 2.0(0.35) ms, SNCV was 53.4±3.0 m/s and the amplitude (SNAPA)was 59.3 (16.4) μV for men and it was 68.7(28.4) μV for women. For the ulnar nerve in men, the DL was 1.85(0.25)ms, SNCV was 55.5 (4.1) m/s and the amplitude(SNAPA) was 55.5 (18.4) μV for men and it was 64.9 (16.8) μV for women. Only the gender showed a statistically significant effect on the sensory nerve action potential for the median (p < 0.04) and the ulnar nerves (p < 0.041). CONCLUSION The normative conduction parameters of the commonly tested nerves in the upper limb were established in our EMG lab. The mean motor nerve conduction parameters for the median and the ulnar nerves correlated favourably with the existing literature data. However, for the sensory nerves, a higher value for the nerve action potential amplitude was demonstrated in this study.

Fasudil hydrochloride ameliorates memory deficits in rat model of streptozotocin-induced Alzheimer’s disease: Involvement of PI3-kinase, eNOS and NFκB

ABSTRACT Restoration of PI3‐kinase signaling portrays therapeutic potential in Alzheimers disease (AD). Hyperactive Rho‐kinase in AD negatively modulates PI3‐kinase pathway, thereby cause cognitive decline. Fasudil is a Rho‐kinase inhibitor that has shown therapeutic benefits in brain disorders. The present study is aimed to decipher the role of PI3‐kinase pathway in neuroprotective activity of fasudil using STZ‐ICV model of AD. MWM and NORT showed that fasudil (300&mgr;g/kg, ICV) averted the STZ‐ICV (3mg/kg) induced memory dysfunctions in rats. Wortmannin (5&mgr;g/rat) or l‐NAME (20mg/kg) attenuated the memory restorative function of fasudil in STZ treated rats. However, l‐Arginine (50mg/kg) group exhibited marked improvement in memory functions. Markers of oxidative stress (TBARS, GSH, SOD, CAT), nitrite, AChE, TNF‐&agr;, eNOS and NF&kgr;B were measured in whole brain of rats. STZ‐ICV group exhibited significant elevation in brain oxidative stress, AChE activity, TNF‐&agr;, NF&kgr;B expression and decrease in eNOS level. These effects of STZ were effectively ameliorated by administration of fasudil for 21 days. Wortmannin (PI3‐kinase inhibitor) or l‐NAME (NOS blocker) attenuated the antioxidative, anti‐inflammatory and cholinergic activities of fasudil. Although brain nitrite content was decreased by l‐NAME and wortmannin, the l‐NAME group depicted rise in eNOS content (not activity) and NF&kgr;B expression, whereas, decrease in same was observed in wortmannin group. l‐Arginine lowered the brain oxidative stress, inflammation, AChE activity, eNOS expression (not activity), NF&kgr;B levels and elevated nitrite content. In STZ‐ICV rat model of AD, fasudil (Rho‐kinase inhibitor) ameliorated the AD symptoms by reinstating PI3‐kinase mediated upregulation of eNOS and control over brain NF&kgr;B activity. HIGHLIGHTSIntracerebroventricular administration of streptozotocin (STZ‐ICV) impaired the spatial and recognition memory in rats.ICV administration of fasudil hydrochloride (fasudil) negated the STZ‐ICV induced rise in oxidative stress, inflammation and acetylcholinesterase activity.The elevation in whole brain endothelial NOS and reduction in NF&kgr;B content by fasudil improved the cognitive abilities in STZ treated rats.Administration of l‐NAME (competitive eNOS inhibitor) and wortmannin (PI3‐kinase inhibitor) impeded the memory revival functions of fasudil in STZ‐ICV treated rats.In the STZ‐ICV model of AD, l‐Arginine treatment potentiated the enhancement of memory by fasudil.