Response variability to ischemic injury in the Mongolian gerbil: an electroencephalographic and behavioral study

The early effects of 5 or 10 min global cerebral ischemia, sham operation and halothane anesthesia were evaluated in Mongolian gerbils by means of electroencephalography (EEG), neurological examination and passive avoidance training. The ischemia-sensitive gerbils (33% and 64% of the 5 and 10 min ischemic groups, respectively) died during carotid ligation or within 24 h; the ischemia-resistant gerbils showed variable behavioral responses. Six hours after ischemia, all of the animals presented EEG activity characterized by increased delta (1–4 Hz) activity and a decreased theta₂ (6–9 Hz) band, with a tendency to recovery at 24 h. Learning impairment was observed in 5 of the 5 min ischemic animals (83%) and in 1 sham (17%) and 1 halothane (17%) control. Fourteen days after ischemia, histologic damage was observed in 4 ischemic gerbils and 1 sham control. On the whole, this study confirms the widely variable susceptibility of gerbils to cerebra ischemia. Moreover, although the variable effects of carotid occlusion have been attributed to multiple factors involving the cerebrovascular system, our data suggest that endogenous cellular mechanisms might protect against ischemia. In view of this consideration, it would be useful to investigate the molecular causes of the variable cerebral ischemic tolerance shown by Mongolian gerbils.Supported by a grant from MURST, Università di Perugia, Italy.     

Kindling in the seizure-prone and seizure-resistant Mongolian gerbil

The kindling response in the amygdala of each of two strains of Mongolian gerbil bred for resistance to and suceptibility to stress-precipitated seizures was assessed. Seizure-prone gerbils had a lower afterdischarge threshold, a longer initial afterdischarge duration, and required fewer sessions to develop generalized kindled convulsions. Following kindling, the precipitated seizure pattern was exacerbated in both groups. These results suggest that the naturally occurring and kindled seizure states may depend in part on a common neural mechanism in this species.     

Projections from the sacculus to the cochlear nuclei in the Mongolian gerbil

The projections of the saccule, an otolith end organ, to the cochlear nuclei were studied using both transganglionic transport and intracellular injection techniques. Labeled fibers and terminals were observed in the anterior and posterior portions of the ventral cochlear nucleus and the dorsal cochlear nucleus. Most terminals were present in the granule cell domain, especially in the subpeduncular corner between the anteroventral cochlear nucleus and the floccular peduncle of the cerebellum. It has been hypothesized that the cochlea in mammals may have developed phylogenetically from the saccule. The projections from the saccule to the cochlear nuclei were investigated in a mammalian species, the Mongolian gerbil, in an attempt to obtain initial information supporting or refuting this hypothesis. The presence of an otolith end organ projection to the cochlear nuclei in rodents should encourage comparative studies in additional aspects of the evolution of the auditory system.     

Age-related changes of gamma-aminobutyric acid transaminase immunoreactivity in the hippocampus and dentate gyrus of the Mongolian gerbil

We investigated the age-related changes of gamma-aminobutyric acid transaminase (GABA-T, a GABA degradation enzyme) in the hippocampus and dentate gyrus of the gerbil at postnatal month 1 (PM 1), PM 3, PM 6, PM 12, and PM 24. Age-related changes of GABA-T immunoreactivity were distinct in the hippocampal CA1 region and in the dentate gyrus. GABA-T immunoreactivity was weak at PM 1, but at PM 3, it had increased significantly, and then increased further. Between PM 6 and PM 12, strong GABA-T immunoreactivity was found in nonpyramidal cells (GABAergic) in the stratum pyramidale of the CA1 region, and at PM 6, strong GABA-T immunoreactivity was found in neurons of the dentate gyrus subgranular zone. At PM 24, CA1 pyramidal cells showed strong GABA-T immunoreactivity. Western blot analysis showed a pattern of GABA-T expression similar to that shown by immunohistochemistry at various ages. In conclusion, our results suggest that the age-related changes of GABA-T provide important information about the aged brain with GABA dysfunction.     

Effects of felbamate on brain polyamine changes following transient cerebral ischemia in the Mongolian gerbil

We sought to determine whether treatment with felbamate was capable to reduce the accumulation of putrescine induced by transient forebrain ischemia in the Mongolian gerbil. Gerbils underwent 10 min ligation of common carotid arteries followed by recirculation. Immediately after the release of the arterial occlusion, felbamate (75 and 150 mg kg(-1) i.p.) was administered. Putrescine and polyamine levels were measured in hippocampus and striatum at 1, 8, 24 and 48 h after recirculation. Putrescine levels appeared enhanced already 8 h after the release of the arterial occlusion and kept increasing up to 48 h in the hippocampus and striatum. No significant changes in spermidine levels during recirculation were detected. Conversely, spermine appeared to decrease in the hippocampus while it did not show changes in the striatum. Felbamate significantly reduced the ischemia induced changes in putrescine brain content only at the dose of 150 mg kg(-1) i.p.     

大鼠脑出血后行为学、组织学及脑水肿相关性研究

目的 探讨胶原酶诱导大鼠脑出血(ICH)后大鼠行为学的改变及其与脑水肿、组织学改变之间的关系.方法 纹状体区立体定向注射胶原酶建立大鼠纹状体ICH模型,动态观察大鼠ICH后28 d内的行为学、组织学及脑含水量改变.行为学评分采用前肢放置实验、Berderson评分法及角落转向实验,组织学观察采用HE染色,脑含水量测定采用干-湿重法.结果 (1)三种行为学试验结果均提示ICH后第2天大鼠出现严重的神经功能障碍,并在4周内神经功能逐渐恢复;(2)组织学观察显示ICH后存在组织损伤和修复过程;(3)脑含水量测定显示ICH后第2天脑水肿最为明显.在14 d内基本消退;(4)ICH后大鼠前肢放置实验评分和脑水肿之间存在负相关(20.774,P<0.05).结论 (1)大鼠ICH后神经功能存在损伤和修复过程;(2)大鼠ICH后神经功能改善仞期与脑水肿消退相关,而后期则可能与组织自身修复过程相关.     

Long-term culture of microvascular endothelial cells derived from Mongolian gerbil brain

A method for long-term culture of microvascular endothelial cells from Mongolian gerbil brain and their biologic properties in vitro are described. Microvessels were isolated from Mongolian gerbil brain by a combination of enzymatic treatment, filtration, and centrifugation and were seeded onto a gelatin-coated dish. A morphologically homogeneous cell plaque showing a cobblestone appearance was removed 2 to 3 weeks after the seeding, and the cells were subcultured. The cultured cells grew as monolayers of flat polygonal cells and were carried for more than 20 passages without morphologic change. These cells synthesized prostacyclin and retained an endothelial specific marker, factor VIII-related antigen. When the cells were cultured in a collagen gel, they rapidly formed capillarylike tubular structures without endothelial cell growth factor or special substrata. Long-term culture of purified microvascular endothelial cells derived from Mongolian gerbil brain will facilitate the study of the function of microvascular endothelial cells in human brain under normal and pathologic conditions.     

Behavioural effects of neocortical and cingulate lesions in the Mongolian gerbil

The experiments examine the effects of cortical lesions on a variety of behaviours in the Mongolian gerbil (Meriones unguiculatus). Gerbils with either large anterior or posterior lesions were compared with normal gerbils by administering a battery of tests of rodent behaviours such as grooming, eating, social interaction, ventral marking and foot-stomping. In a second experiment, a more detailed investigation was carried out of the effects of focal cortical lesions on ventral marking. The results of these experiments suggest that anterior cortical lesions in gerbils give rise to a number of different deficits in behaviour. The results further suggest that cingulate cortex is part of the neural substrate for ventral marking behaviour. The implications of these results for contemporary theories of frontal lobe function are discussed.     

Some effects of early monocular deprivation in the Mongolian gerbil

The effects of short- and long-term early monocular deprivation were investigated in 4 Mongolian gerbils using interocular differences in grating acuity as a measure of deprivation-induced impairment. All gerbils showed acuity deficits in the initially deprived eye, ranging in magnitude from 0.24-1.40 octaves. One month of monocular deprivation from eye opening proved sufficient to induce a permanent acuity impairment.     

Level of ischemia and brain functions in the Mongolian gerbil in vivo

The Mongolian gerbil (Meriones unguiculatus) provides a very useful animal model to study the effects of ischemia on brain functions. In this model it is possible to induce two levels of ischemia in the same animal. Thus, monitoring the brain in vivo in real-time will provide meaningful information regarding the development of ischemic injury as well as the follow-up during the recirculation period. The aims of the study were as follows: (1) To elucidate the mechanism behind the development of ischemic depolarization under unilateral and bilateral carotid artery occlusion. (2) To exclude the possibility that removal of the dura mater will affect the results. (3) To correlate the kinetics of the recovery processes to the level of ischemia. We tested the correlation between energy depletion level (evaluated by intramitochondrial NADH redox state) and the development of ischemic depolarization (ID) and vasospasm (evaluated by extracellular K+, DC potential and 366 nm reflectance changes, respectively) under partial and complete ischemia (induced by unilateral or bilateral carotid artery occlusion) using the multiparametric monitoring system (MPA). In 12 out of 32 gerbils monitored by the MPA, the dura mater remained intact, while in the other 20, it was removed very gently before connecting the MPA to the brain. Two types of responses to unilateral carotid artery occlusion were recorded and the gerbils were divided into groups according to the development of the ID. In a third group of 5 gerbils we tested the effect of 1-5 min of bilateral occlusion on the various parameters monitored.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vasoactive intestinal peptide in the hypothalamohypophysial system of the Mongolian gerbil

By use of the indirect peroxidase-antiperoxidase immunohistochemical technique the location of perikarya and fibers exhibiting vasoactive intestinal peptide (VIP)-like immunoreactivity was investigated in the hypothalamus and the posterior pituitary of the Mongolian gerbil (Meriones unguiculatus), because of the involvement of VIP in several neuroendocrine functions. In the hypothalamus, a large number of VIP-immunoreactive perikarya were seen in the ventromedial part of the suprachiasmatic nucleus. Few VIP-positive perikarya were present in the periventricular, paraventricular, and supraoptic nuclei and in the medial preoptic area close to the third ventricle. The perikarya in the paraventricular nucleus projected fibers in the direction of the median eminence. In the median eminence VIP-immunoreactive fibers were present especially in the external layer, concentrated in the perivascular spaces surrounding the portal vessels. Scattered VIP-immunoreactive fibers were also located in the internal layer of the median eminence as well as in the posterior pituitary lobe. In the latter, large VIP-positive Herring-like bodies were observed. With receptor autoradiography a large number of grains were demonstrated in the anterior pituitary lobe in contrast to the neural lobe. Many VIP-positive fibers and some perikarya were observed within the ependyma covering the rostroventral part of the third ventricle. Finally, fibers exhibiting VIP immunoreactivity were also seen in the organum vasculosum laminae terminalis (OVLT). These results support the concept that VIP is released into the portal vascular system and plays a role in the regulation of the activity of the anterior pituitary. In addition, VIP might be secreted into the cerebrospinal fluid of the third ventricle.     

Histochemistry of MAO-A and MAO-B in the locus coeruleus of the Mongolian gerbil

Summary A coupled peroxidation technique for localization of monoamine oxidase (MAO-A and MAO-B), applied to post-mortem fixed tissue of the locus coeruleus of the Mongolian gerbil is demonstrated. Tyramine hydrochloride,-phenylethylamine and 5-hydroxytryptamine creatinine sulphate were used as substrates, l-deprenyl and clorgyline served as specific inhibitors. All three substrates stained the neurons of locus coeruleus in the absence of inhibitor. In the presence of 1-deprenyl, tyramine hydrochloride and 5-hydroxytryptamine creatinine sulphate were metabolized, whereas in the presence of clorgyline no reaction with either substrate could be observed. Immunocytochemical staining of tyrosine hydroxylase (TH) was employed as comparison.     

Eye and brain growth in the Mongolian gerbil (Meriones unguiculatus)

Eye and brain growth were evaluated by measures of weight and surface dimensions at 11 ages spanning the period from birth to 150 days of age in the Mongolian gerbil (Meriones unguiculatus). Brain weight was found to increase very rapidly until day 18, followed by a more gradual increase to asymptote by 70 days of age. Eye growth follows overall body growth more closely than brain growth. Eye shape was found to change from ovoid to spherical over the first 70 days of life. The possible relationship between eye growth and retinal specialization is considered, and brain growth is compared across several rodent species.     

Grating acuity of the Mongolian gerbil (Meriones unguiculatus)

The grating acuity of the Mongolian gerbil was measured using a two-alternative forced-choice task in a jumping stand. Frequency-of-seeing curves generated by a modified method of limits indicated that the acuity of the gerbil for a horizontal square-wave grating is about 1.5-2.0 cycles/degree (c/deg) at 70 cd/m2, using the 70%- and 80%-correct levels of performance as criteria for defining acuity. The acuity for horizontal gratings is reliably better than that for vertical gratings, and this difference does not appear to be luminance-dependent. A corresponding orientation anisotropy is not seen in acquisition scores, nor is an 'oblique effect' evident. The acuity of the gerbil continues to increase with luminance into the (human) photopic range, suggesting the existence of a functional cone system. The gerbil visual system appears to be well adapted for detail vision in a diurnal lifestyle.     

Effects of radiation on capillary endothelial cells derived from Mongolian gerbil brain]

Confluent monolayers of capillary endothelial cells derived from Mongolian gerbil brain were irradiated with a single exposure of x-rays, and their radiosensitivity and sequential changes in morphology, staining intensity for factor VIII-related antigen (F VIII RAg), and capacity to produce prostacyclin (PGI2) were examined. The radiobiologic parameters that characterized the dose-response survival curve for these cells were found to be n = 1.9, Dq = 140 rad, and D0 = 190 rad. Morphologically, nuclear and cytoplasmic swelling, vacuolation of cytoplasm, and giant cell formation occurred in a dose dependent manner after 24 hours from irradiation. Decreased staining intensity for F VIII RAg was observed in morphologically affected cells. The capacity to synthesize PGI2 was significantly enhanced at 24 hours, but less significant at 72 hours after irradiation. The present data suggest that the radiosensitivity of brain capillary endothelial cells may be somewhat lower than that of endothelial cells originated from larger vessels, and that radiation induced morphological and functional changes in the brain capillary endothelial cells may be quantitatively similar to the changes in endothelial cells of larger vessels.     

The ontogenesis of sensorimotor reflexes in the Mongolian gerbil Meriones unguiculatus.

The ontogeny of a number of sensorimotor reflexes has been studied in the Mongolian gerbil. In contrast to a number of other mammals, the gerbil has relatively long and strong hindlimbs but small forelimbs, indicating their different importance for a number of locomotor acts, and during the developmental period studied, the hindlimbs grow at a much faster rate than the forelimbs. The following sequence of appearance and maturation of the reflexes was observed: rooting, forelimb hopping, surface body righting, forelimb grasp, hindlimb hopping, chin tactile placing, visual placing, air body righting and, at the same time, forelimb and hindlimb tactile placing. This sequence concords with the general gradient of development and maturation of the spinal and brain centers subserving these reflexes, as evaluated from Nissl preparations. The results indicate that there is no clearcut rostro-caudal gradient of postnatal maturation of the spinal cord and the spinally mediated reflexes, but that there is a general caudo-rostral gradient of brain maturation and of the brain-mediated reflexes. Comparisons with other mammals are made.     

Early experience affects seizure latency and postseizure recovery time in the Mongolian gerbil

Seizure prone gerbils reared under low levels of stimulation had shorter seizure latencies than those given extra stimulation from post-natal days 1–21. They also exhibited prolonged postseizure hyperactivity in the open field whereas the latter did not. This provides new evidence that level of cerebral excitability is, in part, a function of early experience. Further, it suggests that seizure activity and its after effects may be mitigated by manipulating the early experience of seizure prone subjects.