Restorative Neurology and Neuroscience - Volume 18, issue 4

Authors: Butovas, Sergejus | Lukkarinen, Jouko | Virtanen, Tiina | Jolkkonen, Jukka | Sivenius, Juhani

Article Type: Research Article

Abstract: Purpose: Tbc present study compared tbc effect of chronic administration of the selective cc2-adrenoceptor antagonist, atipamezole, on performance in behavioral tests that differ in motoric complexity in two experimental stroke models. Methods: Transient occlusion (120 min) of the middle cerebral artery (MCA) using the intraluminal method was used to produce corticostriatal infarcts and permanent occlusion of distal MCA by electrocoagulation was used to produce cortical infarcts. Chronic atipamezole treatment (1 rng/kg, s.c., …once per day) was started 2 days after ischemia induction and continued until the end of the experiment, 35 days after ischemia induction. Behavioral performance of the operated rats was assessed 30 min after drug administration using the limb-placing test and Montoya's staircase test. Results: Atipamezole facilitated spontaneous recovery in the limb-placing task particularly in rats subjected to transient MCA occlusion. The analysis of retrieved pellets in Montoya's staircase test suggests that there is no recovery (Time effect, P > 0.05) in the use of the impaired forelimb (contralateral-to-lesion) following transient MCA occlusion, whereas there was some recovery following permanent MCA occlusion (Time effect, P < 0.001). The impairment was bilateral in rats subjected to transient MCA occlusion. Atipamezole treatment did not affect the use of the impaired forelimb to retrieve pellets following transient MCA occlusion, but there was a tendency to facilitate impaired forelimb use following permanent MCA occlusion (Time*Treatment interaction, P = 0.086). Conclusion: Transient occlusion of the MCA produced a severe, long lasting, and bilateral deficit in skilled forelimb use. Permanent occlusion of the distal MCA was associated with less severe impairment, which was alleviated to some extent by administration of atipamezole. This is in contrast to spontaneous recovery and recovery-enhancing effects of atipamezole in the limb-placing test, particularly in the transient MCA occlusion model. Show more

Keywords: c@2-adrenoceptor antagonist, focal cerebral ischemia, functional recovery, limb-placing, skilled forelimb use

Citation: Restorative Neurology and Neuroscience, vol. 18, no. 4, pp. 143-151, 2001

Authors: Rüthrich, Heide-Linde | Krug, Manfred

Article Type: Research Article

Abstract: Purpose: Moderate normobaric hypoxia causes long-lasting protection against damage induced by a second ischemic or traumatic insult. The changes induced by such conditioning hypoxia are not yet fully understood. The protective effect has been described in various publications but other effects seem possible. Methods: In order to search for effects of conditioning normobaric hypoxia yet unknown, we measured O-Mg++ potentiation and classical long-term potentiation (LTP) in the CA, region of hippocampal slices seven days …after the conditioning procedure. Furthermore, tests were also carried out in chronically implanted rats as to whether LTP was changed in the dentate gyrus after conditioning hypoxia. Results: In slices taken from animals which received conditioning hypoxia, O-Mg++ potentiation and classical LTP of the population spike were significantly enhanced, when compared to population in two control groups. Anoxic LTP, i.e. increase in the population spike of the field potential in the dentate gyrus immediately after finishing the procedure, and a tendency to elevation of LTP seven days after conditioning were also found in chronically implanted animals which were subjected to conditioning hypoxia. Conclusions: lt. may be hypothesized that elevated Ca++ transport in the neurons during conditioning hypoxia is responsible for both long- lasting increases in plastic reactions and the protective effect. Show more

Keywords: Hypoxia, Preconditioning, Hippocampal slices, Long-term potentiation, O-Mg2+, CA l, Dentate gyrus, Perforant pat, Rats

Citation: Restorative Neurology and Neuroscience, vol. 18, no. 4, pp. 153-160, 2001

Authors: Galani, Rodrigue | Hoffman, Stuart W. | Stein, Donald G.

Article Type: Research Article

Abstract: Purpose. The aim of the present study was to assess the effect of different durations of administration of progesterone (4 mg/kg) on the resolution of edema 6 days after medial frontal cortex contusions (MFC) in male adult rats. Methods: Animals sustaining injury were injected with progesterone or its vehicle for 3 days or for 5 days beginning the first hour after surgery. On the 6th day the rats were killed and their brain water content was measured. …Results: We confirmed the presence of edema six days after MFC. However, both 3 and 5 days of treatment with progesterone significantly reduced edema in the injured brains but the five days of treatment were more effective. The effects of progesterone depend upon the duration of the treatment because there are two waves of edema. The first phase begins within a few hours of the injury and the second starts several days later. Conclusions: Our data are consistent with earlier findings showing that longer durations of progesterone administration lead to more complete behavioral recovery as well as to an increased number of surviving neurons. Show more

Keywords: brain injury, edema, frontal cortex, hormones, progesterone, rats, TBI

Citation: Restorative Neurology and Neuroscience, vol. 18, no. 4, pp. 161-166, 2001

Authors: Young, Cara | Miller, Erica | Nicklous, Danielle M. | Hoffman, John R.

Article Type: Research Article

Abstract: Purpose: Many studies have investigated the roles of neurotrophic factors in nerve regeneration by examining either anatomical recovery (regenerated axon count) or functional recovery as measured by sensory and motor behavior. This longitudinal study examined the effects of NGF and NT3 on functional and anatomical recovery following transection of tbc sciatic nerve. Methods: Alzet osmotic pumps were implanted to deliver a continuous supply of NGF, NT3 or buffer solution to the stunips of the transected sciatic …nerve for the first 28 days following implantation. Rats were tested weekly to determine the extent of recovery of motor (footprint gait analysis) or nociceptive (warm water withdrawal), and mechanoreceptive (skin pinch) function. Results: Neither NT3-, nor NGF-treatment significantly enhanced motor recovery as examined by gait analysis. At the end of 12 weeks of behavioral testing, there was no difference in motor recovery. In addition, the recovery of withdrawal response to warm water stimulus was delayed in NGF treated animals. After twelve weeks, nerves were removed for anatomical analysis. Regenerated sciatic nerves from NT3 treated animals had slightly more axons than control- or NGF-treated animals. Conclusion: This work shows that there were no long-lasting improvements of anatomical or functional recovery in NGF- or NT3-treated animals 12 weeks following sciatic nerve transection. Show more

Keywords: regeneration, anatomy, behavior, sciatic

Citation: Restorative Neurology and Neuroscience, vol. 18, no. 4, pp. 167-175, 2001

Authors: Rousseau, V. | Sabel, B.A.

Article Type: Research Article

Abstract: Purpose: Diffuse axonal injury following partial optic nerve crush (ONC) leads to severe visual deficits from which rats can partially recover within 2-3 weeks. To evaluate tbc role of surviving retinal ganglion cells (RGCS) in recovery, we have observed their morphology repeatedly in vivo with ICON-microscopy and correlated cell size changes with recovery of vision which we observed in parallel in the same animals. Methods: After rats had learned a visual contrast discrimination task using an …automated, computer-based test, RGCs were labeled retrogradely with fluorescent beads. Animals then received either no lesion, a complete axotomy or bilateral mild, moderate or severe ONC. Before surgery and for 40 days post-operatively, ROC number and soma size was repeatedly quantified every five days with tbc in vivo confocal neuroimaging method (Sabel et al., Nature med. 3, 1997, p. 244). In parallel, visual function was quantified with the contrast-discrimination task. Results: After ONC about 70 % of the ROCs died after having undergone a fast and massive soma swelling. The extent of cell death was independent of crush severity. RGCs surviving the injury did not change their body size over time in the severe group and these animals also did not recover their vision. In contrast, after a mild or moderate crush, about half of the surviving RGCs experienced a slow and moderate, "compensatory" cell soma swelling and the rats showed partial recovery of vision. Both the number of RGCs showing such compensatory soma swelling and the extent of the swelling correlated highly (r = 0.96) with recovery of contrast discrimination performance at post-operative days 23 and 38. Conclusions., Depending en the time course and extent, soma swelling after neurotrauma may be associated either with cell death or recovery of function. Because of the very high correlation between extent of recovery and amount of soma swelling, moderate soma swelling contributes in a prominent way to recovery of vision. We believe that these cells provide an important structural substrate for neuronal tissue repair and therefore term these cells "compensatory neurons". Show more

Keywords: vision, plasticity, retinal ganglion cells, recovery of function, recovery of vision, ICON, contrast discrimination, neurotrauma, rat

Citation: Restorative Neurology and Neuroscience, vol. 18, no. 4, pp. 177-189, 2001

Authors: Brown, Todd J. | Storer, Paul | Oblinger, Monica | Jones, Kathryn J.

Article Type: Research Article

Abstract: Purpose: We have previously demonstrated that systemic administration of testosterone propionate (TP) can accelerate the functional recovery from hind limb paralysis following sciatic nerve injury in the rat. In this study, we looked at the molecular mechanisms underlying this phenomenon. Methods: Castrated adult male rats received a right side sciatic nerve crush at the level of the sciatic notch, with the left side serving as control. Half the animals received a subcutaneous implant of TP, the …others were sham implanted. Animals were sacrificed at 1, 3, 7 and 10 days post-operative. Lumbar spinal cord tissue was harvested and in situ hybridization was performed using a cytoskeletal cDNA probe complementary to βII-tubulin. Results: On the injured side, sciatic motoneuron tubulin mRNA levels were increased in alt groups at alt time points. At 3 and 7 days post- op, the TP treated group had significantly higher levels of tubulin mRNA. Conclusions: These results suggest that testosterone enhances the rate of regeneration by increasing the neuronal cytoskeletal response after axonal injury. Further, these results, coupled with the results from previous experiments in other rodent models, suggest a common mechanism for gonadal steroid action on regenerating motoneurons across species. Show more

Keywords: androgen, testosterone, sciatic, motoneuron, βII-tubulin, axotomy

Citation: Restorative Neurology and Neuroscience, vol. 18, no. 4, pp. 191-198, 2001