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Biomedical subjects

R K Bhatnagar

Publications and source records attributed to R K Bhatnagar.

12 recordsLinked to original sources
PubMed1979

Distribution of hypertrophied locus coeruleus projection to adult cerebellum after neonatal 6-hydroxydopamine.

Following treatment as neonates with a high subcutaneous dose of 6-hydroxydopamine (6-OHDA), the projections of the locus coeruleus were mapped in the brains of adult rats. This was done using the technique of unilateral lesions in the nucleus followed by simultaneous determinations of norepinephrine (NE) levels, dopamine-beta-hydroxylase (DBH) activity and synaptosomal [3H]NE uptake in various terminal areas. In particular the cerebellum was subdivided into 3 areas in order to assess any changes from normal in the distribution of the hypertrophied noradrenergic projections here. In vehicle-control rats the lesions resulted in an 80--85% loss of NE in the parietal cortex ipsilateral to the lesion and a 15--20% loss contralaterally. In the control cerebellum the locus coeruleus projection, based upon changes in all 3 markers, is distributed 2/3 ipsilaterally and 1/3 contralaterally with the same pattern present in all 3 subregions. The neonatal 6-OHDA treatment resulted in virtually complete loss of noradrenergic terminals in the cerebral cortex. Following neonatal 6-OHDA treatment cerebellar levels of NE, DBH and [3H]NE uptake increased by between 20--60%, with the smallest increases occurring in [3H]NE uptake. In these rats the locus coeruleus accounted for at least 75--80% of the cerebellar noradrenergic parameters. Unlike control rats however, the lesions in these rats produced only ipsilateral decreases in NE and DBH. On the other hand changes in [3H]NE uptake indicated a normal 2/3 ipsilateral, 1/3 contralateral pattern. It is suggested that two separable events occur in the noradrenergic projection to the cerebellum. The first is the regeneration of an increased number of nerve terminals, or sprouting, and the second is a build-up of synaptic vesicles, or collateral accumulation. The sprouting, judging from the [3H]NE uptake data, occurs with apparently normal distribution, but the accumulation of NE and DBH is confined predominantly to the ipsilaterally projecting axon terminals. This may be the consequence of collateral accumulation resulting from the degeneration of the largely ipsilateral coeruleocortical projection.

Animals↗
PubMed1979

Regional development of norepinephrine, dopamine-beta-hydroxylase and tyrosine hydroxylase in the rat brain subsequent to neonatal treatment with subcutaneous 6-hydroxydopamine.

Neonatal rats were injected subcutaneously with 100 mg/kg 6-hydroxydopamine (6-OHDA), or vehicle, on postnatal days 1, 2 and 3. At several times thereafter, determinations of tyrosine hydroxylase (TOH) and dopamine-beta-hydroxylase (DBH) activities, and norepinephrine (NE) concentration were made in the parietal cortex, cerebellum and pons-medulla in order to assess the extent of initial noradrenergic degeneration induced, and the rate of any ensuing regeneration. By the day following completion of the treatment (postnatal day 4), degeneration of noradrenergic terminals in the parietal cortex and cerebellum was very extensive, with NE levels and DBH activities reduced by more than 80%, and TOH activities reduced by 50%. In the parietal cortex noradrenergic degeneration remained virtually complete; and 9 and 70 days postnatal NE concentration and DBH and TOH activities were all decreased by more than 90--95%. In the cerebellum a progressive regeneration and apparent sprouting of NE fibers was observed. By postnatal day 9, NE, DBH and TOH in this tissue had all recovered to near control levels, and by day 70 these measures exceeded control levels by 95%, 115% and 50% respectively. In the pons-medulla, the initial effect of 6-OHDA on any of the measured parameters was negligible. By postnatal day 9 an increase in NE concentration was apparent, which increased further by day 70 to surpass the control level by 70%. At this same time DBH activity was increased by only 15% and TOH activity was unchanged. Separate analysis of the rostral half of the pons, which contains the locus coeruleus, revealed that on day 70 NE and DBH levels were increased much more substantially than in the whole pons-medulla, and TOH activity was also significantly elevated. This data indicates that the initial amount of degeneration induced by the 6-OHDA treatment is similar in both the parietal cortex and cerebellum, but regeneration proceeds only in the cerebellum. This suggests that noradrenergic fiber growth and regeneration in each target tissue is under independent regulation, possibly by the individual target neurons themselves.

Animals↗
PubMed1979

Assessment of the effects of neonatal subcutaneous 6-hydroxydopamine on noradrenergic and dopaminergic innervation of the cerebral cortex.

Female rats, treated at birth with 6-hydroxydopamine (3 x 100 mg/kg s.c. at 24 h intervals) or vehicle, were subjected at 112 days of age to unilateral electrolytic lesions of the locus coeruleus. Two weeks later regions of the telencephalon, both ipsi- and contralateral to the lesion, were simultaneously assayed for norepinephrine (NE) and dopamine (DA) content, and for tyrosine hydroxylase (TOH) and dopamine-beta-hydroxylase (DBH) activities. In the vehicle-treated rats the lesion resulted in at least an 80% reduction of NE and DBH on the ipsilateral side, relative to the contralateral side. TOH was reduced to a similar extent only in the parietal cortex and hippocampus. In the prefrontal cortex and cingulate gyrus TOH was decreased by only 31% and 64% respectively; the remainder was interpreted to be associated with projections of the mesocortical dopamine system. From this data it was possible to calculate that the ratio of TOH to DA in dopaminergic terminals is about 10-fold greater than the ratio of TOH to NE in noradrenergic terminals. Neonatal 6-hydroxydopamine treatment resulted in practically total elimination of noradrenergic terminals throughout the telencephalon, and the locus coeruleus lesion had no additional effect. The drug treatment produced no significant change in DA content or in the TOH to DA ratio in the prefrontal cortex and cingulate gyrus, indicating complete sparing of the mesocortical DA projections.

Animals↗
PubMed1979

Humoral regulation of vascular resistance after 30 days of pulmonary artery constriction.

In an earlier study of guinea pigs with constriction of the pulmonary artery (PA) for 30 days, hindquarters' vascular resistance was maintained primarily by humoral mechanisms. In the present study, we investigated the contribution of circulating catecholamines, angiotensin II, and other constrictor stimuli to hindquarters' vascular resistance by observing vasodilator responses to specific competitive antagonists. Pressure-flow curves indicated vascular resistances in isolated, perfused, sympathectomized hindquarters of anesthetized guinea pigs. Phentolamine produced significantly greater (P less than 0.05) vasodilatation in animals with constriction of pulmonary artery than in sham animals [Sar1-Ala8]angiotensin II produced no vasodilation in either group. After alpha-adrenergic blockade, papaverine produced similar vasodilatation and similar final perfusion pressures in both groups. It appears that circulating catecholamines and augmented vasoconstrictor responsiveness to norepinephrine are totally responsible for the increased humoral regulation of vascular resistance in this experimental model of right ventricular hypertrophy.

Angiotensin II↗
PubMed1978

The effects of subhypnotic doses of ethanol on regional catecholamine turnover.

A 2 g/kg dose of ethanol given intraperitoneally to rats significantly reduced the turnover of dopamine in the substantia nigra and caudate nucleus, increased dopamine turnover in the olfactory tubercle and had no effect on dopamine turnover in the nucleus accumbens, amygdala and hypothalamus. The same dose of ethanol decreased the probenecid-induced homovanillic acid accumulation in the caudate nucleus. The turnover of norepinephrine was also decreased in hypothalamus and increased in the pons medulla region. No change in norepinephrine turnover was observed in frontal cortex, parietal cortex, cerebellum, amygdala, hippocampus and locus ceruleus region. The distribution of ethanol was similar in cortex, caudate nucleus, hypothalamus and pons-medulla. Catecholamine turnover in different brain regions seems to be differentially sensitive to the effects of ethanol, with most regions being unaffected by ethanol.

Animals↗
PubMed1977

Histochemical and biochemical characterization of the rat paracervical ganglion.

The nature and identity of the catecholamines in the paracervical ganglion and superior cervical ganglion small, intensely fluorescent (SIF) cells were investigated using fluorescence histochemical and immunohistochemical techniques. The paracervical ganglion SIF cells were found to contain norepinephrine and the superior cervical ganglion SIF cells, dopamine. The norepinephrine content of the paracervical ganglion SIF cells averaged about 72 ng/ganglion and did not change during the rat estrus cycle. The activity of the enzyme tyrosine hydroxylase in the PCG was very low (about 0.48 nmoles DOPA formed/h/mg protein) and was about 1/50th of the activity of the enzyme in the SCG, where it averaged about 23.90 nmoles DOPA formed/h/mg protein. These experiments suggested that the paracervical ganglion has large numbers of norepinephrine containing SIF cells with a relatively slow turnover of their catecholamine content.

Adrenal Medulla↗
PubMed1975

Differentiation between stains of human blood and blood of monkey.

The precipitin tube test fails to differentiate between blood stains of closely related animals such as man and monkey because of the close similarity between antigenic determinants of serum proteins of such closely related species. The quantitative precipitin technique cannot be applied to forensic work. This paper cites a case where definite opinion on the species of origin of some blood stains suspected to have come from a monkey was possible. In the method used, extracts of the questioned stain were tested with similar extracts of known human and known monkey blood stains against human globulin antiserum, by comparative double diffusion method in agar gel on microslides.

Animals↗