Albert A. Lamperti

The effect of neonatally administered monosodium glutamate (MSG) on the development of retinofugal projections and the entrainment of circadian locomotor activity

The acute administration of monosodium- l -glutamate (MSG, 8 mg/g) to neonatal hamsters ( Mesocricetus auratus ) destroys the neurons of the inner retina, although some ganglion cells survive. Despite the severe optic nerve degeneration, MSG-treated hamsters synchronize their circadian locomotor activity to light:dark signals. The central projections of the surviving ganglion cells in these animals were determined using anterograde tracing techniques. The retinohypothalamic pathway responsible for the photic synchronization of the locomotor activity was unaffected by the neurotoxin, although the remaining visual pathways were markedly reduced. The results indicate a differential sensitivity of retinal ganglion cells to MSG. The resistance of the retinal ganglion cells that innervate the suprachiasmatic nucleus of the hypothalamus to neonatal MSG treatment is discussed in relationship to other findings. The results from this study and other physiological and morphological findings suggest that the retino-hypothalamic system is an anatomically independent component of the optic system.

Effects of Hydrocephalus and Surgical Decompression on Cortical Norepinephrine Levels in Neonatal Cats

Norepinephrine (NE) changes during hydrocephalus, and the effects of surgical decompression on these changes, were studied using a new model of neonatal hydrocephalus. Kittens 4 to 10 days old received intracisternal injections of a sterile solution of 25% kaolin. Control kittens were injected similarly with sterile injectable saline. Ultrasonography was used to follow the progression of ventriculomegaly and the initial effects of the shunts. A subgroup of hydrocephalic animals was shunted using a cerebrospinal fluid lumbar-peritoneal catheter. Hydrocephalic animals were killed at approximately 25 days of age (16-21 days after kaolin injection). Surgical decompression was performed at 12, 16, and 17 days after kaolin injection; these animals were killed 30 days after the shunts were inserted. Control animals were killed at 29 and 53 days of age, to correlate with the ages of the hydrocephalic and shunted animals, respectively. Cortical samples equivalent to Brodmanns areas 4, 22, and 17 were measured for NE using high-performance liquid chromatography. Hydrocephalus caused NE levels to decrease significantly in all cortical areas. These alterations followed a rostrocaudal gradient in severity, with mean reductions of 65.8, 83.9, and 95.8% in areas 4, 22, and 17, respectively. Partial recovery occurred in animals that received shunts 16 and 17 days after kaolin injection, such that NE reductions of 75.7, 56.2, and 81.6% were noted in areas 4, 22, and 17, respectively. Shunting at 12 days after kaolin injection produced complete recovery in areas 4 and 22, with only a 67.7% decrease in area 17. These results suggest that the projection fibers from the locus ceruleus are damaged by the direct effects of hydrocephalus. Axotomy or neuropraxia of these fibers could result in decreases in NE throughout the cerebral cortex. In addition, there appears to be a period of time during which surgical decompression will allow neuropraxic fibers to recover with partial restoration of NE levels. Earlier insertion of a shunt appears to allow for more recovery than later decompression.

Monoamine alterations during experimental hydrocephalus in neonatal rats

The present study was designed to determine the selected monoamine changes that occur during infantile hydrocephalus. Obstructive hydrocephalus was induced in newborn rats by injection of a suspension of kaolin into the 4th ventricle and cisterna magna. Eleven days later, experimental animals and their sham-operated littermate controls were killed and pieces of frontoparietal cortex, neostriatum, cerebellar vermis, and brain stem were processed for high performance liquid chromatography. Grossly, the lateral ventricles were extremely enlarged, the cerebral cortex was thinned, the neostriatum was compressed, and portions of the tectum and cerebellum were vacuolated. Decreases in norepinephrine (71%), dopamine (73%), and serotonin (50%) were observed in the cerebral cortex, neostriatum, and cerebellum, respectively. Brain stem norepinephrine and serotonin were increased 70% and 50%, respectively. These increases may indicate impairment of axonal transport or damage to projections from the locus ceruleus and raphe region. These preliminary results suggest that infantile hydrocephalus causes perturbations in the levels of different monoamines in several brain regions. Such changes may critically influence neuronal function and development, as well as the therapeutic management of hydrocephalus.

Computer‐based neuroanatomy laboratory for medical students

To present the laboratory portion of our first‐semester Human Neuroanatomy course at Temple University Medical School more effectively and efficiently and to replace the glass slide/microscope‐based laboratory component of the course, we developed a computer‐based substitute.

The effects of mercury on the structure and function of the hypothalamo-pituitary axis in the hamster.

SummaryThe neurons of the arcuate nucleus were studied ultrastructurally in female hamsters that were given saline or 1 mg mercuric chloride/day during one estrous cycle. Membranous whorls, composed of 4–26 concentric layers of smooth endoplasmic reticulum, were found in 7–8% of the neurons of control animals in diestrus (D3) and in proestrus (D4). Whorls were found in 5–16% of the neurons in mercury-treated animals on all days of the experimental period. The whorls appeared to be associated with RER and Golgi bodies. The levels of FSH and LH were measured in the plasma and pituitaries of both groups of animals. There was a significantly higher concentration of FSH in the pituitaries of experimental animals on D3 and of LH on D1C2 of the subsequent cycle; plasma levels of FSH and LH were similar in both groups throughout the experimental period. The relationship between the levels of gonadotropins and the presence of membranous whorls is discussed.

Alterations in Insulin and Glucagon Secretion by Monosodium Glutamate Lesions of the Hypothalamic Arcuate Nucleus

This study was performed to determine the effects of monosodium glutamate (MSG) induced lesions of the hypothalamic arcuate nucleus (ARC) on glucose tolerance and insulin and glucagon secretion in male golden hamsters. Eight day old hamsters were given a single s.c. injection of 5.8 mg/g BW MSG or hypertonic saline (controls). Studies were initiated when the hamsters were 3 months of age. At this age there were no body weight differences. Glucose (180 mg/100 g BW) was administered via stomach tube to 18 control and 18 MSG-treated hamsters. Animals were anesthetized with ether and a single blood sample from the portal vein was taken either before or at 30 or 60 min after glucose administration (n = 6/group). Glucose concentrations were similar in both groups at all time periods. Insulin concentrations in the MSG group were significantly (P less than 0.05) elevated in MSG-treated hamsters compared to controls at the 60 min time point. Glucose suppressed glucagon (P less than 0.05) in control but not in MSG-treated hamsters. The MSG group had significantly more glucagon (P less than 0.05) in portal vein blood at 30 min after glucose administration than did the control hamsters. Molar insulin/glucagon ratios did not differ between the 2 groups which likely accounts for the lack of differences in blood glucose levels. These results suggest a role for the ARC in regulating pancreatic function.

Tonicity of resuscitative fluids influences outcome after spinal cord injury.

OBJECTIVE This investigation was designed to test the hypothesis that the tonicity of resuscitative fluids administered after spinal cord injury influences the magnitude of secondary injury and, therefore, outcome. METHODS Rat spinal cords were compressed with 50 g of weight for 5 minutes to produce injury. After spinal cord injury, the animals were randomized into three experimental groups. Group 1 (n = 10) received no fluid resuscitation after spinal cord injury. Group 2 (n = 6) received 5 ml/kg of intravenously administered Ringer’s lactate 1 minute after the removal of compression. Group 3 (n = 7) was treated with 5 ml/kg of intravenously administered 7.5% hypertonic saline 1 minute after the removal of compression. Neurological outcome was assessed daily for 10 days using the Basso, Beattie, and Bresnahan locomotor rating scale. Histological evaluations of the spinal cord were obtained on Day 10. RESULTS The average number of recovery days before the rats were able to spontaneously void their bladders was significantly less (P < 0.05) in the hypertonic saline-treated group. Spontaneous hindlimb movement also occurred sooner in the hypertonic saline-treated animals. The average neurological score was significantly higher (P < 0.05) in the hypertonic saline-treated group during each of the 10 days of recovery. Histological evaluation supported the finding of attenuation of injury in the hypertonic saline-treated animals. CONCLUSION The results of this investigation with a chronic model of spinal cord injury support the contention that hypertonic saline treatment may provide protection to the spinal cord after mechanical injury.

Transdermal absorption of radioprotectors using permeation-enhancing vehicles

Radioprotectors are not currently used clinically due to concerns regarding toxicity and uncertainties regarding tumor protection. Topical radioprotection of skin might find clinical applications with protectors such as WR-2721, but laboratory studies in which protectors have been applied in water have not been promising. We have studied the absorption of 14C-WR-2721 and [14C]cysteine dissolved in skin permeation-enhancing vehicles through the skin of hairless mice and compared the absorption to that in water. Skin concentration of WR-2721 was increased most by dimethylformamide (DMF), but only propylene glycol increased absorption as far as the dermis, as measured by plasma concentration. Skin concentration of cysteine was improved by DMF, 2-pyrrolidone (2-P), and methyl-2-pyrrolidone (M-2-P); only dimethylsulfoxide (DMSO) resulted in increased plasma levels of the protector. Pretreating skin with DMSO before application of WR-2721, irrespective of the vehicle, improved its concentration within the skin. Plasma levels were improved (10 and 12 times) only with 2-P and DMF. Therefore, by choosing the appropriate vehicle, it is possible to breach the barrier of the stratum corneum and enhance the presence of the protector in all layers of the skin.

Transdermal Absorption of Radioprotectors in the Rat Using Permeation-Enhancing Vehicles

Topical radioprotection of rat skin with WR-2721 has not been effective presumably because the drug does not cross the stratum corneum to reach the epidermis and dermis. Earlier, we showed in the mouse that WR-2721 and cysteine dissolved in permeation-enhancing vehicles passed through the skin more readily than when in water. However, the most effective vehicles in the mouse were not necessarily as effective in the rat. Here we report that the most effective transport vehicles in the rat were (1) water with WR-2721, (2) water and dimethylformamide (DMF) with cysteine, and (3) water and DMF with prostaglandin E2 (PGE2). Pretreatment of the skin with dimethylsulfoxide (DMSO) further improved the transfer of the radioprotectors across the skin in most cases. After pretreatment with DMSO, the most effective vehicles were (1) water for WR-2721, (2) water and methyl-2-pyrrolidone (M-2-P) for cysteine, and (3) DMF for PGE2.

Pituitary Responsiveness to LHRH Stimulation in Hamsters Treated Neonatally with Monosodium Glutamate

Previous studies have shown that neonatal administration of monosodium glutamate (MSG) results in a clearly defined lesion of the arcuate nucleus which disrupts mechanisms regulating normal FSH but not LH secretion in the adult female hamster. The present study was designed to investigate the effects of neonatally administered MSG or hypertonic saline (control) on the in vivo and in vitro responses to LHRH in adult animals. In order to evaluate these responses under a comparable hormonal background, all animals were ovariectomized at 2-3 months of age and given 50 micrograms of estradiol benzoate 3 weeks later. 24 h later, animals were anesthetized with sodium pentobarbital and a blood sample taken for baseline levels of gonadotropins; they were immediately given 5 or 25 ng LHRH intravenously, and LH and FSH responses to LHRH were determined by sampling at 15-min intervals over a 1-hour period. Pituitary content of LH and FSH was determined in a similar group of control and MSG-treated animals which did not receive the hypothalamic hormone. Basal LH secretion, the dose-response of LH to LHRH, and the pituitary concentration or content were similar in control and MSG-treated hamsters. In contrast to LH, basal FSH levels were significantly lower, the FSH responses to LHRH were greatly attenuated, and a dose response to LHRH was absent in MSG-treated animals when compared to control values. Pituitary FSH concentration and content did not differ between control and MSG-treated animals. However, when pituitaries were removed, hemidissected, preincubated for 1 h, and incubated in the presence or absence of 8.5 x 10(-9) or 8.5 x 10(-10) M LHRH for 3 consecutive 1-hour periods, no differences were noted between control and experimental animals regarding basal (no LHRH) or LHRH-stimulated release of LH and FSH. These results suggest that the decreased basal FSH levels and the attenuated FSH response to LHRH observed in vivo in MSG-treated animals may be due to an alteration in a neural or extraneural component which is involved in regulating the release of FSH by LHRH and which is evident in the absence of a functional arcuate nucleus and/or develops directly as the result of the neonatal administration of MSG.