Early social isolation provokes electrophysiological and structural changes in cutaneous sensory nerves of adult male rats.

Sensory and social deprivation from the mother and littermates during early life disturbs the development of the central nervous system, but little is known about its effect on the development of the peripheral nervous system. To assess peripheral effects of early isolation, male rat pups were reared artificially in complete social isolation (AR); reared artificially with two same-age conspecifics (AR-Social); or reared by their mothers and with littermates (MR). As adults, the electrophysiological properties of the sensory sural (SU) nerve were recorded. We found that the amplitude and normalized area (with respect to body weight) of the compound action potential (CAP) response provoked by single electrical pulses of graded intensity in the SU nerves of AR animals were shorter than the CAP recorded in SU nerves from MR and AR-Social animals. The slope of the stimulus-response curve of AR SU nerves was smaller than that of the other nerves. The histological characterization of axons in the SU nerves was made and showed that the myelin thickness of axons in AR SU nerves was significant lower (2-7µm) than that of the axons in the other nerves. Furthermore, the area and axon diameter of SU nerves of both AR and AR-Social animals were significant lower than in MR animals. This is the first report to show that maternal and littermate deprivation by AR disturbs the development of the myelination and electrophysiological properties of axons in the SU nerve; the replacement of social cues prevents most of the effects.

Functional and morphological effects of repeated sodium arsenite exposure on rat peripheral sensory nerves.

Exposure to inorganic arsenic (iAs) is known to result in peripheral neuropathy. To better understand the functional and morphological consequences of iAs exposure, we examined the electrophysiological and histological characteristics of the sensory sural nerves in adult Male Wistar rats following 30 days of sodium arsenite administration by gavage (10 mg/kg body weight/day). Arsenic (As) levels in the peripheral nerves of exposed animals were about 150 times greater than those in controls. Lipid peroxidation was also increased in iAs-exposed animals. Compound action potentials (CAPs) evoked in iAs-exposed nerves were characterized by a slower conduction velocity ( approximately 26%). iAs-exposed nerves also showed a trend towards a decreased CAP area ( approximately 35%). These electrophysiological changes were consistent with histological alterations such as a approximately 56% decrease in myelin thickness. In addition, the perimeter and transverse area of axons were reduced to 29% and 45% of control, respectively. Our results suggest that accumulation of As produced by iAs exposure induces oxidative damage, severe demyelination, and other morphological alterations in axons of peripheral nerves. These changes may, in turn, induce changes in the generation and propagation of action potentials in peripheral nerves, leading to decreased transmission of information from peripheral sensory organs to the central nervous system.

Hindlimb claudication reflects impaired nitric oxide-dependent revascularization after ischemia.

Although vascular remodeling is important in preventing tissue damage and restoring muscle function, there is no evidence of a relationship between vascular remodeling and muscle function after peripheral vascular occlusion. Nitric oxide (NO) has been implicated in the process of vascular remodeling in hindlimb ischemia. Thus, development of alterations in hindlimb gait after ischemia may be associated with impaired nitric oxide-dependent, vascular blood flow recovery. We evaluated hindlimb gait as an index of ischemia-induced revascularization and tested the effects of NO synthase inhibition on both hindlimb blood flow and hindlimb gait locomotion. After 14 days of ischemia, the ischemic hindlimb showed no significant differences in gait locomotion compared to the sham-operated hindlimb. However, hindlimb ischemia drastically reduced hindlimb blood flow from 46+/-3 mL/min/100 g to 12+/-2 mL/min/100 g which reverted to 33+/-5 mL/min/100 g after 14 days of ischemia. eNOS mRNA expression levels at 3, 7, 14, and 28 days after initiation of ischemia, were increased by 50+/-5%, 100+/-10%, 140+/-8% and 270+/-12% respectively and eNOS protein expression levels at 7, 14, and 28 days, were increased by 28+/-3%, 62+/-6% and 80+/-16% respectively. However, eNOS inhibition caused by l-NAME treatment prevented blood flow recovery and correction of abnormal gait locomotion in rats. Thus, the duration of the stride-swing phase increased and the stride length decreased. The knee joint angle decreased during flexion and extension with eNOS inhibition. In conclusion, ischemia-induced revascularization is associated with recovery of both hindlimb blood flow and normal gait locomotion. Moreover, prevention of NO synthesis, a key messenger in ischemia-induced revascularization, is associated with impairment in hindlimb locomotion. Thus, gait locomotion represents a functional model that could be used to evaluate the degree of ischemia-induced revascularization.

Absence of linear correlation between fluctuations in area of simultaneous recorded monosynaptic responses and Hoffmann's reflexes in the rat.

In this study we analyze the possible relationship between fluctuations in area of monosynaptic reflex responses (MSR) and Hoffmann's reflex (H reflexes) in the plantar closed loop pathway of the anesthetized rat. These reflexes were evoked by low-frequency stimuli applied to the sciatic nerve or lateral plantar nerve and then concurrently recorded on the distal tibial nerve or lateral plantar nerve, respectively as well as the lateral plantar muscles in the foot of the anesthetized rat. From trial to trial, H reflexes showed higher variability in area than MSR, whether the latter was recorded in the distal tibial nerve (n=8 experiments) or in the lateral plantar nerve (n=5 experiments). No linear correlation was found between changes in area of concurrently evoked MSR and H reflexes (r(MSR-H,n=8)=0.11+/-0.03 and r(MSR-H,n=5)=0.08+/-0.09, respectively). These findings suggest that trial-to-trial fluctuations in area of H reflexes may involve interaction of several sources of variation, among others to MSR variability (due to pre-, and post-synaptic factors influencing the excitability of spinal motoneurons) in combination with those related to peripheral mechanisms, such as trial to trial activation of a different number of muscle fibers, either by the probabilistic transmitter release from neuromuscular junctions, by activation of motor units of variable size or to fluctuations in excitability of muscle fibers.

Lipid oxidative damage and distribution of inorganic arsenic and its metabolites in the rat nervous system after arsenite exposure: influence of alpha tocopherol supplementation.

Inorganic arsenic (iAs) exposure causes peripheral neuropathy. Oxidative effects caused by iAs exposure in peripheral nerves have been incompletely characterized. This study analyzed arsenic and lipid oxidative damage in the brain, spinal cord, and sciatic and sensory sural nerves following arsenite exposure. This study also explored whether alpha tocopherol (alpha-TOC) administration mitigates arsenite-induced oxidative damage. Thiobarbituric acid-reactive substance (TBARS) levels and distributions of iAs and its metabolites were evaluated in male Wistar rats following 30d of sodium arsenite exposure (10mg/kg bodyweight (bw)/d, by gavage). A second group also received alpha-TOC (125mg/kg bw/d, by gavage) during the final 20d of arsenite administration. Arsenite exposure caused increased TBARS levels within each region of the nervous system; oxidative stress was most pronounced in the sural and sciatic nerves. In addition there was a positive quadratic relationship between TBARS levels and the concentration of arsenicals found in the nervous system (r(2)=0.878, p<0.001). Dimethylarsenic was the predominant metabolite of iAs found. Animals alpha-TOC-treated had a 1.7-5.2-fold reduction in TBARS levels when compared with rats that received iAs alone. These results suggest that oxidative damage may be the main mechanism of toxicity induced by exposure of the peripheral nervous system to arsenite and that such damage could be attenuated by alpha-TOC-supplementation.