A comparative analysis of the cerebral cortical proteins in rats with different sensitivities to hypoxia]

A comparative analysis of 339 protein fractions of cerebral cortex of rats both resistant and non-resistant to oxygen deficiency has been fulfilled by means of two-dimensional gel-electrophoresis. A specific group of 9 protein fractions with molecular weights in the range of 32-68 kD was found to be quantitatively changed under hypoxia influence. An activation of labile protein synthesis was a predominant response to acute hypoxia in the resistant rats, while the synthesizing processes in the non-resistant rats were rather weak. An adaptation to hypoxia mostly resulted in the decrease of quantitative representations of labile protein fractions and has been realizing in different ways in resistant and nonresistant rats. The data obtained seem to testify to the changes of protein synthesis under chronic hypoxia conditions in the cerebral cortex chiefly determined by fast adaptation mechanisms.     

Stimulation of the rat's sciatic nerve regeneration by local treatment with Xymedon

1. The possibility of a neuro-protective effect of Xymedon as a pharmacological stimulator of nerve regeneration has been studied through Schwann cells (SCs) located in the potential area of regenerating nerve fibers' growth. 2. Xymedon was injected into the silicone chamber connecting the central and peripheral stumps of the rat's sciatic nerve. Carboxymethyl cellulose was used as a depositioned medium. 3. A 0.95% concentration of Xymedon increased the sciatic nerve functional index (SFI) values on the 14th, 21st and 28th day after the operation. By day 30, the total number of survival neurons in the L5 dorsal root ganglion (DRG) on the ipsilateral side increased with the following changes in Xymedon concentration: [see text] The number of surviving sensory neurons in the group with 0.95% Xymedon increased by 36% (p < 0.05) compared with animals with depositioned medium but Xymedon free. 4. It is suggested that the positive effects of Xymedon on neural regeneration and recovery of motor function support the potential use of Xymedon for the treatment of peripheral nerve injuries.     

Stimulation of cerebral cortical synaptosomal Na-K-ATPase by biogenic amines.

The amines noradrenaline, dopamine, 5-hydroxytryptamine, and histamine (0.01-0.5 mM) enhanced the activity of Na-K-ATPase (EC 3.6.1.3) in rat cerebral cortical synaptosomal fractions. The activities of Mg-ATPase and Ca-Mg-ATPase were not significantly affected. No stimulation of Na-K-ATPase occurred in the presence of chelating agents (0.5 mM EGTA or EDTA) unless 0.5 mM calcium had also been added to the incubation medium. These results are consistent with the hypothesis that amines depress cerebral cortical neurones by activation of an electrogenic sodium pump. Calcium ions appear to be involved in this process.     

White adipose tissue sensory nerve denervation mimics lipectomy-induced compensatory increases in adiposity

The sensory innervation of white adipose tissue (WAT) is indicated by the labeling of sensory bipolar neurons in the dorsal root ganglion after retrograde dye placement into WAT. In addition, immunoreactivity (ir) for sensory-associated neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P in WAT pads also supports the notion of WAT sensory innervation. The function of this sensory innervation is unknown but could involve conveying the degree of adiposity to the brain. In tests of total body fat regulation, partial surgical lipectomy triggers compensatory increases in the mass of nonexcised WAT, ultimately resulting in restoration of total body fat levels in Siberian hamsters and other animals. The signal that triggers this compensation is unknown but could involve disruption of WAT sensory innervation that accompanies lipectomy. Therefore, a local and selective sensory denervation was accomplished by microinjecting the sensory nerve neurotoxin capsaicin bilaterally into epididymal WAT (EWAT) of Siberian hamsters, whereas controls received vehicle injections. Additional hamsters had bilateral EWAT lipectomy (EWATx) or sham lipectomy. As seen previously, EWATx resulted in significantly increased retroperitoneal WAT (RWAT) and inguinal WAT (IWAT) masses. Capsaicin treatment significantly decreased CGRP- but not tyrosine hydroxylase-ir, attesting to the diminished and selective sensory innervation. Capsaicin-treated hamsters also had increased RWAT and, to a lesser degree, IWAT mass largely mimicking the WAT mass increases seen after lipectomy. Collectively, these data suggest the possibility that information related to peripheral lipid stores may be conveyed to the brain via the sensory innervation of WAT.     

The effect of active substances on nerve fiber regeneration in nerve tissue cultures

Explants of the ganglion trigeminale from chick embryos and hippocampi from embryonal rats were incubated in maximowchambers with semisynthetic media. The different parts of nervous tissue were influenced experimentally by addition of biological extracts and by substances with known composition. The regeneration of nerve fibers was investigated by the index of growth. The growth index was calculated from the ratio of nerve fibre index of the test cultures to that of the influenced cultures. Under these conditions biological extracts enhanced the growth of nerve fibres. In the same way the growth of nerve fibres was statistically significantly stimulated by substances with known composition of aminoacids, orotic acid, sodium orotate and cyclic monophosphates. A stimulating effect of cyclic guanosinmonophosphate seems to exist only in CNS explants and only in young fetal rats and consists in an increased migration and proliferation of cells as well as in the formation of fibres from neuroblasts. The investigations gave strong evidence for the in vitro testing to be very useful in studies of nerve fibre regeneration. However the choice of suitable reference systems, suitable quantitative parameters, optimal concentration and periods of application of effective substances and the age of the animals are of fundamental importance for the evaluation of the results. Experiments regarding the stimulation of the differentiation of neurons and the growth of nerve fibres are of practical clinical and therapeutical interest.     

Stimulation of post-traumatic regeneration of x-irradiated skeletal muscles in old rats

Regeneration in murine musculus gastrocnemius was studied in animals aged 2-2.5. It was demonstrated that 20Cy irradiation caused the inhibition of necrosis resorption, suppressed the proliferative activity of muscular and connective tissues. Impulse laser therapy employed after irradiation of dissected musculus gastrocnemius potentiated fibrin resorption and markedly stimulated regeneration of muscular and connective tissues. Nonexposed disintegrated muscular tissue, when implanted to the site of injury produced a significant stimulating effect resulting in necrosis resorption, more pronounced than under laser therapy, and recovering the regenerative capacity of the exposed tissue.     

Effect of substance P on nerve fiber regeneration in tissue culture

Explants of the ganglion trigeminale from chick embryos (PNS) and of the hippocampus from fetal rats (CNS) were cultivated in maximow chambers with growth medium or maintanance medium. Varied concentrations of substance P (SP . 3 CH3COOH . 4 H2O) were added. 1. The effect of substance P (SP) is related to concentration. In the presence of 10(-7)M SP in the growth medium and of 10(-4)M SP in the maintanance medium the cultivation of PNS cultures indicates positive results. These doses are suitable. 2. Within the first 24 hours in vitro SP stimulates the index of area in PNS cultures. The index of characterizes the relation of the outgrowth zone to the explant. In CNS cultures a significant difference of this effect was not observed. 3. The index of growth of nerve fibers may compare the test cultures with the control cultures. SP significantly increases the index of fiber growth in PNS cultures. A stimulation of CNS cultures was observed, significance was not found. 4. From the beginning of the cultivation with SP up to 48 hours in vitro the growth of nerve fibers significantly increases in the treated cultures in comparison with the control cultures. After this time the growth of nerve fibers decreased and a morphological conformity of test cultures and controls was observed. 5. The role of SP is discussed in specific activity on PNS tissue in vitro. The reactive neurons may be from the medio dorsal group of cells of the sensible ganglion.     

The peripheral nerve allograft: an assessment of regeneration across nerve allografts in rats immunosuppressed with cyclosporin A

Lewis rats (RT1(1] were the recipients of 3-cm nerve grafts from syngeneic Lewis donors or allogeneic ACI (RT1a) donors. Microneurosurgical repair of the nerve graft to the transected sciatic nerve of the recipient animal was performed with 10-0 epineurial sutures. Recipients were randomly allocated to cyclosporin A (CsA) immunosuppressed or untreated groups. Cyclosporin A was administered in the minimal effective dosage to prevent nerve allograft rejection across this major histocompatibility disparity (5 mg/kg per day). Nerve regeneration across the nerve grafts was assessed by sciatic function index (SFI) and toe spread index (TSI) determinations serially and by electrophysiologic, histologic, and morphologic assessments 14 weeks after engraftment. Sciatic nerve regeneration across allogeneic nerve grafts in cyclosporin A immunosuppressed recipients was significantly superior compared to the untreated controls (p less than 0.008) and not significantly different from that across the syngeneic control animals.     

A conditioning lesion promotes in vivo nerve regeneration in the contralateral sciatic nerve of rats

A conditioning lesion in the sciatic nerve increases in vivo axonal regeneration in the nerve after a second transection. We studied whether this increased regeneration also occurs in the contralateral nerve. The left sciatic nerve was transected and sutured in Wistar rats; the nerve was exposed but not transected in controls. After 5 days, the right sciatic nerves of all rats were transected and sutured. Neuronal regeneration was measured at 0, 1, 3, 5, and 7 days with the pinch test and histological staining. IL-1beta and TGF-beta1 expression was also measured. The initial delay in the experimental group was significantly shorter, but the regeneration rates were the same. The expression of IL-1beta and TGF-beta1 in the right dorsal root ganglia was significantly higher in the experimental group. Nerve injury enhances cytokine expression in the contralateral dorsal root ganglion and promotes contralateral nerve regeneration in vivo by shortening the initial delay.     

脑缺血和缺血再灌注大鼠皮层神经元自噬的动态变化

目的：探讨脑缺血和缺血/再灌注不同时间大鼠大脑皮层神经元自噬的变化。方法：健康雄性SD大鼠60只,随机分为：假手术（Sham）组（n=10）,脑缺血和缺血/再灌注模型组（n=50）.模型组分别在缺血30min、2h,缺血2h再灌注1h、6h、24h五个时间点,随机抽取10只大鼠,测定脑梗死体积和脑含水量,同时采用Western印迹法测定各组大鼠大脑皮层中微管相关蛋白轻链3-Ⅱ（LC3-Ⅱ）的水平,透射电镜检测大脑皮层神经细胞自噬情况。结果：脑缺血30min时LC3-Ⅱ/Ⅰ比值未见明显上升,缺血2h时LC3-Ⅱ/Ⅰ比值开始升高,明显高于Sham组（P<0.01）;缺血/再灌注1h、6h时LC3-Ⅱ/Ⅰ比值虽较缺血2h组有所下降,但仍明显高于Sham组（P<0.05）;缺血/再灌注24h时LC3Ⅱ/Ⅰ比值达高峰,明显高于Sham组（P<0.01）。透射电镜观察进一步证实该现象。缺血/再灌注6h和24h时大鼠脑梗死体积明显增加,与Sham组比较有统计学差异（P<0.01）。缺血/再灌注24h大鼠脑组织含水量明显增加,明显高于Sham组（P<0.05）。HE染色显示：仅在缺血/再灌注24h组大鼠皮层见组织水肿、疏松,部分细胞变性、凋亡,海马区见大量神经元细胞核皱缩、深染呈变性凋亡状。结论：局灶性脑缺血和缺血/再灌注模型中大脑皮层缺血2 h神经元自噬即明显激活,缺血/再灌注1 h、6 h自噬均持续增高,缺血/再灌注24 h自噬达高峰。     

Pretreatment of rats with pulsed electromagnetic fields enhances regeneration of the sciatic nerve

Regeneration of the sciatic nerve was studied in rats pretreated in a pulsed electromagnetic field (PEMF). The rats were exposed between a pair of Helmholtz coils at a pulse repetition rate of 2 pps at a field density of 60 or 300 μT. The PEMF treatment was then discontinued. After an interval of recovery, regeneration of the sciatic nerve was initiated by a crush lesion. Regeneration of sensory fibers was measured by the “pinch test” after an additional 3–6 days. A variety of PEMF pretreatments including 4 h /day for 1–4 days or exposure for 15 min/day during 2 days resulted in an increased regeneration distance, measured 3 days after the crush lesion. This effect could be demonstrated even after a 14-day recovery period. In contrast, pretreatment for 4 h/day for 2 days at 60 μT did not affect the regeneration distance. The results showed that PEMF pretreatment conditioned the rat sciatic nerve in a manner similar to that which occurs after a crush lesion, which indicates that PEMF affects the neuronal cell body. However, the mechanism of this effect remains obscure. © 1993 Wiley-Liss, Inc.     

Modulation of vibrissa-evoked cortical potentials after infraorbital nerve crush in rats

Cortical potentials evoked by unilateral stimulation of the major vibrissae were recorded in 12 rats subjected to unilateral crush of the infraorbital nerve. Immediately after nerve crushing, the latency of the initial positive potential evoked at contralateral scalp sites by stimulating the vibrissae of the nerve-crushed side was increased. In contrast, the latency of the ipsilaterally evoked potential was shortened. The relative amplitude of the negative component to the positive one of the evoked potentials tended, immediately after the nerve crush, to be smaller on the contralateral cortex (N/P-contra) and greater on the ipsilateral cortex (N/P-ipsi). These changes disappeared largely by the 2nd post-operative week. It is suggested that reduction of the tactile signals transmitted through the crossed pathway is responsible for the prolonged latency and the smaller N/P-contra. Shortening of the ipsilateral latency and the enhanced N/P-ipsi may be due to liberation of the ipsilateral sensory system from inhibition by the contralateral one.     

Hepatic cytochrome P-450 in chronically hypoxemic rats

The basal level of hepatic cytochrome P-450 and its inducibility by phenobarbital pretreatment have been found to be enhanced by chronic hypoxemia. Pentobarbital sleeping times were decreased in parallel to changes in levels of cytochrome P-450. The increase in level of hepatic cytochrome P-450 in chronically hypoxemic rats occurred despite the increased levels of hepatic heme oxygenase which previously were associated with the chronic hemoglobinemia of the hypoxemic state. Chronically hypoxemic rats may provide a useful model for study of control of hepatic heme and hemoprotein metabolism.