预变神经段修复神经缺损的实验研究

目的探讨不同预变时间组移植神经对神经再生的影响。方法以ＳＤ大鼠的不同预变时间组的尺神经作为移植神经，修复其正中神经的缺损。实验侧按移植神经预变时间的不同分为０、１、２、３、４、８周共６组，每组６只ＳＤ大鼠。移植后１２周，检测实验侧趾屈肌群的张力、最大收缩力、再生神经的形态及神经轴突的截面积。结果用预变１周的尺神经修复正中神经后，其趾屈肌群的张力及最大收缩力的恢复率达到正常对照组的８１．１％及８５．９％。显微镜下观察，预变１周组和其它各时间组相比，其再生的神经轴突最多，发育最成熟。结论用预变１周的神经段修复神经缺损，其神经再生能力最佳     

Primary brain stem lesions caused by closed head injuries

Traumatic lesions of the brain stem are of two types: primary, which are considered to be caused at the moment of impact, and secondary, associated with supratentorial mass lesion. Of the 239 patients with a serious head injury who showed a severe disturbance of consciousness upon admisision and who had CT scan carried out immediately, 21 cases were considered to have a primary brain stem lesion with initial CT scan. A primary brain stem lesion was found in 21 of 239 (8.8%) of patients with serious head injury. Their injuries were caused primarily by traffic accidents. Sixteen of the 21 cases showed not only brain stem lesions but also other brain injuries such as cerebral contusion of the white and gray matter, callosal injury, intraventricular hemorrhage, and subarachnoid hemorrhage, which are considered to be caused by a diffuse shearing injury. Five cases who showed a single injury to the brain stem with no other brain lesions were considered to have a pure brain stem lesion. Primary brain stem lesions were observed on the dorsal side of the midbrain, where they can be differentiated from secondary brain stem lesions. These lesions are considered to result from the shearing mechanism in and around the brain stem very close to the tentorial edge, or to an injury of the lower brain stem by hyperextension of the cervical vertebrae. The prognosis of patients with a primary brain stem lesion was usually unfavorable, except in those with a single brain stem lesion.     

The relation between conduction velocity and axonal length

Motor evoked potentials (MEPs) obtained by electrical root stimulation and F waves were used to examine the proximal nerve conduction velocity (CV) to tibialis anterior (TA), extensor digitorum brevis (EDB), flexor carpi radialis (FCR), and abductor pollicis brevis (APB) muscles in 40 humans. By subtracting motor latencies obtained by stimulating the peripheral nerve at the same point from the F-wave and MEP latencies, we could measure the CV over identical proximal segments. It was found that proximal CV to TA and FCR was significantly higher than to EDB and APB, respectively. Combining the data of the proximal CV to all four muscles in relation with axonal length resulted in a highly significant inverse relationship (r² = 0.77). Thus the axonal length explained to a large extent the higher CV of the arm nerves and also the inverse relation between body height and CV. The distal CV was always lower than proximal CV; however, there was no support for an additional effect of this gradient in explaining the relationship between CV and height since it was constant for all body heights. © John Wiley & Sons, Inc.     

Axonal domains within shared touch domes in the rat: a comparison of their fate during conditions favoring collateral sprouting and following axonal regeneration

Low-threshold mechanosensory nerves in the adult rat differ both from their counterparts in lower vertebrates and from high-threshold nociceptive nerves in mammals in that they appear not to undergo collateral sprouting into adjacent denervated skin, although they will clearly regenerate into it after they are damaged. We have now studied the growth capabilities of the low-threshold nerves supplying touch domes, the visible mechanosensory structures scattered throughout the hairy skin. Touch domes in the rat are often multiply innervated. A serendipitous observation on such domes allowed us to investigate the possibility that a functional collateral sprouting of their nerves can indeed occur, but only to a spatially very restricted extent, e.g., within the confines of a partially denervated dome. We used a "prodder" with a tip diameter of 16 micron to examine the mechanosensory profile across single domes that were preselected as being supplied by only two axons, one running in each of two adjacent dorsal cutaneous nerves (DCNs). Simultaneous recordings were made of the afferent discharges evoked in these nerves when the prodder was applied at about 17 or more locations on a selected dome; the spatial resolution was better than 55 micron. We found that within such a shared dome, one axon can supply a discrete territory (its "domain"), which may or may not overlap with the corresponding domain of the other axon. In a preliminary electron microscopic study, we found no evidence for a sharing of single Merkel cells, which are the specialized sensory cells in touch domes, even in the regions of a shared dome where two domains overlapped; each innervated Merkel cell appeared to be contacted by a single nerve ending, implying that in a shared dome each axon probably supplies an exclusive subpopulation of the Merkel cells. We tested for functional collateral sprouting by eliminating one nerve to a shared dome, and at a selected time thereafter mapping the domain of the remaining axon to see whether it had enlarged. The result was the same whether the two domains initially had a region of overlap or not; no expansion of the surviving domain occurred over postoperative periods up to 4 months (an expansion of the domain by 55 micron would have been detected). Thus functional collateral sprouting had failed to occur.(ABSTRACT TRUNCATED AT 400 WORDS)     

Normal and regenerating optic fibers in goldfish tectum: HRP-EM evidence for rapid synaptogenesis and optic fiber-fiber affinity

The distribution of normal and regenerating retinal fibers and synapses was studied on tectum in goldfish by light (LM) and electron microscopy (EM). Since labeling of the early regenerating fibers was previously reported to be difficult, a new 'cold-fill' HRP labeling protocol was developed, which labeled regenerating optic fibers and terminals on tectum as early as 14 days after nerve crush when they first arrive on tectum. In order to characterize the laminar distribution of optic afferents in normal fish and in fish regenerating for 14-240 days, EM photomontages of areas 14 microns wide by 160 microns deep through the HRP-labeled primary optic innervation layer (S-SO-SFGS) were constructed. The time points in regeneration that were examined spanned the period in which others have shown that an initially diffuse retinotopic map becomes spatially restricted. At the LM level regenerating optic fibers were restricted to the optic lamina. They reinnervated tectum in an anterior to posterior sequence as previously seen with autoradiography. In addition, at 14 days, some "pioneer" optic fascicles were found to have already grown to posterior tectum where they gave rise to branches with boutonlike terminations and growth-cone-like processes. Form the ultrastructural analysis it was clear that optic fibers and terminals observed strict laminar boundaries as they partitioned themselves in the optic laminae (S, SO and SFGS) in both normal and regenerating fish. The behavior of optic fibers was lamina specific with respect to synapse formation and the orientation of fiber outgrowth. As early as 14 days regeneration, optic fibers made synapses onto the four types of postsynaptic profiles observed in normal fish. Numerous optic terminals were labeled at 14 days, and there appeared to be no waiting period between fiber ingrowth to the SO and synapse formation in the S and SFGS. At 14-60 days, atypical synaptic contacts which appear to be nascent synapses were made by labeled optic fibers in fascicles and by growth-cone-like processes. By 21-30 days, the density of optic terminals was high and there were many more fasciculated optic fibers in the SFGS than normal as late as 350 days. These findings suggest that optic fiber lamination is highly constrained by tectal cues, that fibers rapidly regenerate many synaptic terminals before retinotopic map refinement is complete, and that fibers have a strong affinity for each other.     

Protection of chlordecone-potentiated carbon tetrachloride hepatotoxicity and lethality by partial hepatectomy

Chlordecone (CD) pretreatment is known to markedly potentiate CCl₄ hepatotoxicity. Previous studies have shown that prior exposure to CD obtunds the increased hepatocellular regeneration and repair observed in non-treated rats challenged with a single, low dose of CCl₄. These observations allowed us to hypothesize that suppression of hepatic regeneration and tissue repair by CD + CCl₄ combination treatment might be involved in this interaction. To test this hypothesis, CCl₄ hepatotoxicity was evaluated in actively regenerating livers using CD-treated (10 ppm in the diet for 15 days), surgically partially hepatectomized (PH) male Sprague-Dawley rats. Rats undergoing no surgical manipulation (CTRL) and sham operation (SH) were included as appropriate controls. Surgical manipulations were conducted on day 15 of the dietary protocol. Based on liver-to-body weight ratios (LW/BW), mitotic indices, hepatic cytochrome P-450 content, and hepatic glutathione (GSH and GSSG) levels, PH-induced hepatocellular regeneration was not affected by pretreatment with CD. Thus, the PH model was considered valid for assessing the effects of CD + CCl₄ combination treatment. CCl₄ (100 l/kg; i.p.) was administered 1, 2, 4 or 7 days after the surgical manipulations. Hepatotoxicity was assessed 24 h later by measuring LW/BW and serum enzymes (SGPT, SGOT and ICD) in all four groups. Hepatic histopathological, histomorphometric and lethal effects were assessed in animals receiving CCl₄ 1 or 7 days after the surgical manipulations. CCl₄-induced increases in LW/BW were observed in CD + PH rats receiving CCl₄ 4 or 7 days post-PH, but not in the 1 or 2 day post-PH groups in which the hepatocellular regeneration was maximal. CCl₄-induced serum enzyme elevations were significantly less in the CD + PH rats as compared to CD + SH. This decrease in the serum enzyme elevations was most prominent in the 1 day post-PH group, where the hepatocellular mitotic activity was most pronounced. CCl₄ lethality, assessed in the 1 day post-surgical manipulation group, was also decreased in the CD + PH rats in comparison to CD + SH rats. Such a protection was not observed in rats receiving CCl₄ 7 days post-PH. These data are consistent with and are supportive of the hypothesis that a suppression of otherwise normally stimulated hepatocellular regeneration following low-dose CCl₄ administration is involved in the marked amplification of CCl₄ toxicity by CD.Abbreviations CD chlordecone - GSH reduced glutathione - GSSG oxidized glutathione - PH partial hepatectomy - SH shamhepatectomy - CTRL control, not surgically manipulated - N normal diet - LW/BW liver weight-to-body weight ratio - SGPT serum glutamic; pyruvic transaminase - SGOT serum glutamic oxaloacetic transaminase - ICD isocitrate dehydrogenase These studies were made possible by a grant from the US Environmental Protection Agency R-811072A preliminary report of these findings was presented at the 70th Annual Meetings of the Federation of American Societies for Experimental Biology at St. Louis, MO (Fed Proc 45: 1051, 1986)A. N. Bell is a Predoctoral Toxicology Trainee and Robert A. Young is a Postdoctoral Trainee supported by Toxicology Training grant from National Institute of Environmental Health Science ES-07045     

Comparative study of suture and laser-assisted anastomoses in rat sciatic nerves

Conventional suture repair of peripheral nerves results in a fibrotic reaction that is detrimental to nerve regeneration. As an alternative procedure known as "laser-assisted" repair, a laser can be used, along with a reduced number of sutures, to reanastomose served peripheral nerves. To explore the long-term implications of this technique, the right sciatic nerves of Sprague-Dawley rats were surgically cut and reanastomosed either by means of four epineurial sutures or two epineurial sutures and CO2 laser welds. Tensile strength, electrophysiology, histology, and functional studies were performed up to 11 months postoperatively. Tensile strength measurements indicate no long-term disadvantage with the laser-assisted technique, although the short-term tensile strength is lower than with conventional suture repair. The conduction velocities of the repaired nerves were similar for both techniques; however, laser-assisted repaired nerves were found to have lower stimulation thresholds and reduced branching compared to the suture repaired nerves. The measured functional recovery was similar for both repair techniques.     

Acceleration of peripheral nerve regeneration after crush injury in rat

It the sciatic nerve of a rat is crushed in the thigh, axons from the proximal side of the crush will regenerate so that the toe-spreading reflex becomes observable again after 10.4 +/- 1.7 (mean +/- S.D.) days. If the nerve is electrically stimulated for 0.25-1.0 h at the crush site, just after the crush occurs, the toe-spreading reflex first becomes observable 4.14 +/- 1.6 (mean +/- S.D.) days after the crush. Stimulation is most effective if delivered immediately after the crush but can be delayed up to an hour and still cause significantly faster regeneration. This phenomenon could be useful in clinical management of crushed peripheral nerves.