Effect of Centella asiatica on cognition and oxidative stress in an intracerebroventricular streptozotocin model of Alzheimer's disease in rats.

1. Centella asiatica, an Indian medicinal plant, has been described as possessing central nervous system activity, such as improving intelligence. In addition, we have demonstrated that C. asiatica has cognitive-enhancing and anti-oxidant properties in normal rats. Oxidative stress or an impaired endogenous anti-oxidant mechanism is an important factor that has been implicated in Alzheimer's disease (AD) and cognitive deficits seen in the elderly. 2. Intracerebroventricular (i.c.v.) streptozotocin (STZ) in rats has been likened to sporadic AD in humans and the cognitive impairment is associated with free radical generation in this model. Therefore, in the present study, the effect of an aqueous extract of C. asiatica (100, 200 and 300 mg/kg for 21 days) was evaluated in i.c.v. STZ-induced cognitive impairment and oxidative stress in rats. 3. Male Wistar rats were injected with STZ (3 mg/kg, i.c.v.) bilaterally on the days 1 and 3. Cognitive behaviour was assessed using passive avoidance and elevated plus-maze paradigms on the days 13, 14 and 21. Rats were killed on the day 21 for estimation of oxidative stress parameters (malondialdehyde (MDA), glutathione, superoxide dismutase and catalase) in the whole brain upon completion of the behavioural task. 4. Rats treated with C. asiatica showed a dose-dependent increase in cognitive behaviour in both paradigms. A significant decrease in MDA and an increase in glutathione and catalase levels were observed only in rats treated with 200 and 300 mg/kg C. asiatica. 5. The present findings indicate that an aqueous extract of C. asiatica is effective in preventing the cognitive deficits, as well as the oxidative stress, caused by i.c.v. STZ in rats.

Effect of Centella asiatica on pentylenetetrazole-induced kindling, cognition and oxidative stress in rats.

Cognitive impairment in epileptics may be a consequence of the epileptogenic process as well as antiepileptic medication. Thus, there is a need for drugs, which can suppress epileptogenesis as well as prevent cognitive impairment. In the present study, the effect of aqueous extract of Centella asiatica (CA) (100 and 300 mg/kg), an Indian medicinal plant known to possess antiepileptic, cognitive-enhancing and antioxidant property, was evaluated on the course of kindling development, kindling-induced learning deficit and oxidative stress markers in pentylenetetrazole (PTZ) kindled rats. Male Wistar rats were injected PTZ (30 mg/kg ip) once every alternate day (48+/-2 h) until the development of the kindling. Passive avoidance test and spontaneous locomotor activity were carried out 24 and 48 h after the last administration of PTZ, while the oxidative stress parameters (malondialdehyde [MDA] and glutathione) were carried out in the whole brain upon completion of the behavioral assessment. The administration of CA (300 mg/kg orally) decreased the PTZ-kindled seizures and showed improvement in the learning deficit induced by PTZ kindling as evidenced by decreased seizure score and increased latencies in passive avoidance behavior. However, low dose of the CA (100 mg/kg) showed improvement only in the learning deficit due to the kindling and failed to improve the seizure score. The findings suggest the potential of aqueous extract of CA as adjuvant to antiepileptic drugs with an added advantage of preventing cognitive impairment.

Intracerebroventricular administration of colchicine produces cognitive impairment associated with oxidative stress in rats.

Oxidative stress has been implicated in neurodegenerative disorders including the Alzheimer's disease (AD). Central administration of colchicine is known to cause cognitive impairment in rats and is likened to sporadic AD in humans. However, it is not known whether this cognitive impairment is associated with free radical generation. Therefore, in the present study, the effect of intracerebroventricular colchicine was studied on paradigms of learning and memory behavior and the markers of oxidative stress in rats. Adult male Wistar rats (200-250 g) were injected with colchicine (intracerebroventricular) bilaterally (15 microg/rat; 7.5 microg/site) on the first day. The learning and memory behavior was assessed using passive avoidance paradigm, elevated plus maze and closed field activity test on Days 13, 14 and 21. The parameters of oxidative stress were assessed by measuring the malondialdehyde (MDA), glutathione, superoxide dismutase (SOD) and catalase levels in brain tissue on Day 21 of the colchicine injection. The rats developed significant learning and memory impairment as indicated by deficit in behavioral paradigms. There was a significant elevation in MDA levels and decrease in levels of glutathione. No significant difference was observed in SOD and catalase levels. Thus, the study demonstrates that central administration of colchicine causes impairment in learning and memory with associated increase in oxidative stress.

Effect of different extracts of Centella asiatica on cognition and markers of oxidative stress in rats.

Centella asiatica, a plant mentioned in Indian literature has been described to possess CNS effects such as stimulatory-nervine tonic, rejuvenant, sedative, tranquilizer and intelligence promoting property. In the present study aqueous, methanolic and chloroform extracts of C. asiatica were investigated for their effect on cognitive functions in rats. Male Wistar rats of 200-250 g were used to study the effect on learning and memory by using shuttle box, step through, step down and elevated plus maze paradigms. Only the aqueous extract of whole plant (200 mg/kg for 14 days) showed an improvement in learning and memory in both shuttle box and step through paradigms. Therefore, further experiments were conducted with aqueous extract using 100, 200 and 300 mg/kg doses in different paradigms of learning and memory. All doses of aqueous extract increased the number of avoidances in shuttle box and prolonged the step through latency in step through apparatus in a dose dependent manner, while only two doses 200 and 300 mg/kg of aqueous extract showed significant increase in the step down latency in step down apparatus and transfer latency (TL) in elevated plus maze. Among doses of aqueous extract tested on oxidative stress parameters, only 200 and 300 mg/kg showed a significant decrease in the brain levels of malondialdehyde (MDA) with simultaneous significant increase in levels of glutathione. There was a significant increase in the levels of catalase at the 300 mg/kg but no significant change in superoxide dismutase (SOD) levels were observed. The present findings indicate that the aqueous extract of C. asiatica has cognitive enhancing effect and an antioxidant mechanism is involved.

Inclusion body myositis (IBM).

Clinical, histological, immunohistochemical and ultrastructural features of 5 cases of inclusion body myositis -4 sporadic (s-IBM) and one hereditary (h-IBM) form are described. These patients (3 men, 2 women) had chronic progressive weakness of varying severity in all 4 extremities with sparing of cranial muscles. Elevation of CPK was noted in 2 patients. Electromyography revealed features of myopathy in 4 and additional neurogenic changes in 2 subjects. Clinical diagnosis was often other than inclusion body myositis. Presence of characteristic eosinophilic inclusions within the vacuoles established the diagnosis. The inclusions were congophilic and showed positivity to ubiquitin, beta-amyloid and SMI-31 in the sporadic cases while congophila was absent in the hereditary form. Immunostaining to hyperphosphorylated-tau was negative in both s-IBM and h-IBM. Membraneous whorls were observed at ultrastructural level. None of the patients improved with steroids and trial with other immunosuppressants was unsuccessful.

Chronic inflammatory demyelinating polyneuropathy : clinical, electrophysiological and morphological study.

Twelve patients (M:F 9:3) who fulfilled diagnostic criteria of chronic inflammatory demyelinating polyneuropathy (CIDP) were seen at NIMHANS over a period of three years (1987-1990). Their ages ranged from 20 yrs to 71 yrs and the mean duration of symptoms was 30 months (range 3 months to 6 yrs). Symptoms at the onset were dependent on the duration of disease. These included paraesthesia (7), weakness (4) and ataxia in lower limbs (1). Salient features on examintion were: distal weakness (10), proximal weakness (6), impaired touch and pain (12), impaired joint position and vibration sense (6), distal areflexia (12), bilateral impaired hearing (2) and thickened nerves (4). Electrophysiological evidence of demyelination was present in all and albumino cytological dissociation in CSF was noted in 55 of the patients. Sural nerve biopsy revealed significant loss of myelinated fibres in all the five patients studied. Increase in endo and perineural collagen, remyelination and schwann cell proliferation were also seen. Inflammatory infiltrates were conspicuously absent. Steroids were given in 10 patients. The therapeutic response was good in 5 and moderate in 5. Two patients had remitting relapsing course. Response to steroids could not be predicted on the basis of clinical or laboratory features. The recent diagnostic criteria and their therapeutic relevance are discussed.