The Experts below are selected from a list of 315 Experts worldwide ranked by ideXlab platform
Harry G. Goshgarian - One of the best experts on this subject based on the ideXlab platform.
-
Diaphragmatic recovery in rats with cervical Spinal Cord injury induced by a theophylline nanoconjugate: Challenges for clinical use
Journal of Spinal Cord Medicine, 2019Co-Authors: Yanhua Zhang, Janelle Schafer, Harry G. GoshgarianAbstract:Context: Following a Spinal Cord Hemisection at the second cervical segment the ipsilateral hemidiaphragm is paralyzed due to the disruption of the rostral ventral respiratory group (rVRG) axons de...
-
Systemic administration of rolipram increases medullary and Spinal cAMP and activates a latent respiratory motor pathway after high cervical Spinal Cord injury.
Journal of Spinal Cord Medicine, 2016Co-Authors: Satkunendrarajah Kajana, Harry G. GoshgarianAbstract:Background/Objective: High cervical Spinal Cord Hemisection interrupts descending respiratory drive from the rostral ventral respiratory group in the medulla to the ipsilateral phrenic motoneurons. Hemisection results in the paralysis of the ipsilateral hemidiaphragm. Chronic administration of rolipram, a specific phosphodiesterase-IV inhibitor, promotes synaptic plasticity and restores phrenic nerve function after a high cervical Spinal Cord lesion. Here, we test the hypothesis that an acute administration of rolipram will increase Spinal and medullary levels of 3′,5′-cyclic adenosine monophosphate (cAMP) and induce phrenic nerve recovery after cervical (C2) Spinal Cord Hemisection.
-
ipsilateral inspiratory intercostal muscle activity after c2 Spinal Cord Hemisection in rats
Journal of Spinal Cord Medicine, 2015Co-Authors: Beth M Zimmer, Joshua S Grant, Angelo E Ayar, Harry G. GoshgarianAbstract:AbstractBackgroundUpper cervical Spinal Cord Hemisection causes paralysis of the ipsilateral hemidiaphragm; however, the effect of C2 Hemisection on the function of the intercostal muscles is not clear. We hypothesized that C2 Hemisection would eliminate inspiratory intercostal activity ipsilateral to the injury and that some activity would return in a time-dependent manner.MethodsFemale Sprague Dawley rats were anesthetized with urethane and inspiratory intercostal electromyogram (EMG) activity was reCorded in control rats, acutely injured C2 hemisected rats, and at 1 and 16 weeks post C2 Hemisection.ResultsBilateral reCordings of intercostal EMG activity showed that inspiratory activity was reduced immediately after injury and increased over time. EMG activity was observed first in rostral spaces followed by recovery occurring in caudal spaces. Theophylline increased respiratory drive and increased intercostal activity, inducing activity that was previously absent.ConclusionThese results suggest that th...
-
adenosinergic mechanisms underlying recovery of diaphragm motor function following upper cervical Spinal Cord injury potential therapeutic implications
Neurological Research, 2005Co-Authors: Kwaku D. Nantwi, Harry G. GoshgarianAbstract:Abstract Objectives: In adult rats, a latent respiratory motor pathway can be pharmacologically activated with 1,3-dimethylxanthine (theophylline) to restore respiratory-related activity to a hemidiaphragm paralysed by an ipsilateral upper cervical (C2) Spinal Cord Hemisection. The purpose of this review is to describe mechanisms that underlie theophylline-induced recovery of respiratoryrelated function following C2 Hemisection and to underscore the therapeutic potential of theophylline therapy in Spinal Cord injured patients with respiratory deficits. Methods: Theophylline mediates recovery of respiratory-related activity via antagonism of central adenosine A1 receptors. When administered chronically, the drug restores and maintains recovered function. Since theophylline is an adenosine receptor antagonist with affinity for both the adenosine A1 and A2 receptors, we assessed the relative contributions of each receptor to functional recovery. While A1 receptor antagonism plays a predominant role, activati...
-
theophylline induced respiratory recovery following cervical Spinal Cord Hemisection is augmented by serotonin 2 receptor stimulation
Brain Research, 2002Co-Authors: Gregory J Basura, Kwaku D. Nantwi, Harry G. GoshgarianAbstract:Abstract Cervical Spinal Cord Hemisection leads to a disruption of bulboSpinal innervation of phrenic motoneurons resulting in paralysis of the ipsilateral hemidiaphragm. We have previously demonstrated separate therapeutic roles for theophylline, and more recently serotonin (5-HT) as modulators to phrenic nerve motor recovery; mechanisms that likely occur via adenosine A1 and 5-HT2 receptors, respectively. The present study was designed to specifically determine if concurrent stimulation of 5-HT2 receptors may enhance motor recovery induced by theophylline alone. Adult female rats (250–350 g; n=7 per group) received a left cervical (C2) Hemisection that resulted in paralysis of the ipsilateral hemidiaphragm. Twenty-four hours later rats were given systemic theophylline (15 mg/kg, i.v.), resulting in burst recovery in the ipsilateral phrenic nerve. Theophylline-induced recovery was enhanced with the 5-HT2A/2C receptor agonist, (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI; 1.0 mg/kg). DOI-evoked augmentation of theophylline-induced recovery was attenuated following subsequent injection of the 5-HT2 receptor antagonist, ketanserin (2.0 mg/kg). In a separate group, rats were pretreated with ketanserin, which did not prevent subsequent theophylline-induced respiratory recovery. However, pretreatment with ketanserin did prevent DOI-induced augmentation of the theophylline-evoked phrenic nerve burst recovery. Lastly, using immunocytochemistry and in situ hybridization, we showed for the first time a positive co-localization of adenosine A1 receptor mRNA and immunoreactivity with phrenic motoneurons of the cervical ventral horns. Taken together, the results of the present study suggest that theophylline may induce motor recovery likely at adenosine A1 receptors located at the level of the Spinal Cord, and the concurrent stimulation of converging 5-HT2 receptors may augment the response.
Kwaku D. Nantwi - One of the best experts on this subject based on the ideXlab platform.
-
theophylline treatment improves mitochondrial function after upper cervical Spinal Cord Hemisection
Experimental Neurology, 2010Co-Authors: Maik Huttemann, Kwaku D. Nantwi, Syed Mohiuddin, Theodor PetrovAbstract:Abstract The importance of mitochondria in Spinal Cord injury has mainly been attributed to their participation in apoptosis at the site of injury. But another aspect of mitochondrial function is the generation of more than 90% of cellular energy in the form of ATP, mediated by the oxidative phosphorylation (OxPhos) process. Cytochrome c oxidase (CcO) is a central OxPhos component and changes in its activity reflect changes in energy demand. A recent study suggests that respiratory muscle function in chronic obstructive pulmonary disease (COPD) patients is compromised via alterations in mitochondrial function. In an animal model of cervical Spinal Cord Hemisection (C2HS) respiratory dysfunction, we have shown that theophylline improves respiratory function. In the present study, we tested the hypothesis that theophylline improves respiratory function at the cellular level via improved mitochondrial function in the C2HS model. We demonstrate that CcO activity was significantly (33%) increased in the Spinal Cord adjacent to the site of injury (C3-C5), and that administration of theophylline (20 mg/kg 3x daily orally) after C2HS leads to an even more pronounced increase in CcO activity of 62% compared to sham-operated animals. These results are paralleled by a significant increase in cellular ATP levels (51% in the hemidiaphragm ipsilateral to the Hemisection). We conclude that C2HS increases energy demand and activates mitochondrial respiration, and that theophylline treatment improves energy levels through activation of the mitochondrial OxPhos process to provide energy for tissue repair and functional recovery after paralysis in the C2HS model.
-
differential expression of adenosine a1 and a2a receptors after upper cervical c2 Spinal Cord Hemisection in adult rats
Journal of Spinal Cord Medicine, 2007Co-Authors: Theodor Petrov, Christian W Kreipke, Warren J Alilain, Kwaku D. NantwiAbstract:BACKGROUND: In an animal model of Spinal Cord injury, a latent respiratory motor pathway can be pharmacologically activated via adenosine receptors to restore respiratory function after cervical (C2) Spinal Cord Hemisection that paralyzes the hemidiaphragm ipsilateral to injury. Although Spinal phrenic motoneurons immunopositive for adenosine receptors have been demonstrated (C3-C5), it is unclear if adenosine receptor protein levels are altered after C2 Hemisection and theophylline administration. OBJECTIVE: To assess the effects of C2 Spinal Cord Hemisection and theophylline administration on the expression of adenosine receptor proteins. METHODS: Adenosine A1 and A2A receptor protein levels were assessed in adult rats classified as (a) noninjured and theophylline treated, (b) C2 hemisected, (c) C2 hemisected and administered theophylline orally (3x daily) for 3 days only, and (d) C2 hemisected and administered theophylline (3x daily for 3 days) and assessed 12 days after drug administration. Assessment of A1 protein levels was carried out via immunohistochemistry and A2A protein levels by densitometry. RESULTS: Adenosine A1 protein levels decreased significantly (both ipsilateral and contralateral to injury) after C2 Hemisection; however, the decrease was attenuated in hemisected and theophylline-treated animals. Attenuation in adenosine A1 receptor protein levels persisted when theophylline administration was stopped for 12 days prior to assessment. Adenosine A2A protein levels were unchanged by C2 Hemisection; however, theophylline reduced the levels within the phrenic motoneurons. Furthermore, the decrease in A2A levels persisted 12 days after theophylline was withdrawn. CONCLUSION: Our findings suggest that theophylline mitigates the effects of C2 Hemisection by attenuating the C2 Hemisection-induced decrease in A1 protein levels. Furthermore, A2A protein levels are unaltered by C2 Hemisection but decrease after continuous or interrupted theophylline administration. The effects on protein levels may underlie the stimulant actions of theophylline.
-
involvement of peripheral adenosine a2 receptors in adenosine a1 receptor mediated recovery of respiratory motor function after upper cervical Spinal Cord Hemisection
Journal of Spinal Cord Medicine, 2006Co-Authors: Elysia James, Kwaku D. NantwiAbstract:AbstractBackground/Objective: In an animal model of Spinal Cord injury, a latent respiratory motor pathway can be pharmacologically activated through central adenosine A1 receptor antagonism to restore respiratory function after cervical (C2) Spinal Cord Hemisection that paralyzes the hemidiaphragm ipsilateral to injury. Although respiration is modulated by central and peripheral mechanisms, putative involvement of peripheral adenosine A2 receptors in functional recovery in our model is untested. The objective of this study was to assess the effects of peripherally located adenosine A2 receptors on recovery of respiratory function after cervical (C2) Spinal Cord Hemisection.Methods: Respiratory activity was electrophysiologically assessed (under standardized reCording conditions) in C2-hemisected adult rats with the carotid bodies intact (H-CBI; n = 12) or excised (H-CBE; n = 12). Animals were administered the adenosine A2 receptor agonist, CGS-21680, followed by the A1 receptor antagonist, 1, 3-dipropyl-...
-
adenosinergic mechanisms underlying recovery of diaphragm motor function following upper cervical Spinal Cord injury potential therapeutic implications
Neurological Research, 2005Co-Authors: Kwaku D. Nantwi, Harry G. GoshgarianAbstract:Abstract Objectives: In adult rats, a latent respiratory motor pathway can be pharmacologically activated with 1,3-dimethylxanthine (theophylline) to restore respiratory-related activity to a hemidiaphragm paralysed by an ipsilateral upper cervical (C2) Spinal Cord Hemisection. The purpose of this review is to describe mechanisms that underlie theophylline-induced recovery of respiratoryrelated function following C2 Hemisection and to underscore the therapeutic potential of theophylline therapy in Spinal Cord injured patients with respiratory deficits. Methods: Theophylline mediates recovery of respiratory-related activity via antagonism of central adenosine A1 receptors. When administered chronically, the drug restores and maintains recovered function. Since theophylline is an adenosine receptor antagonist with affinity for both the adenosine A1 and A2 receptors, we assessed the relative contributions of each receptor to functional recovery. While A1 receptor antagonism plays a predominant role, activati...
-
theophylline induced respiratory recovery following cervical Spinal Cord Hemisection is augmented by serotonin 2 receptor stimulation
Brain Research, 2002Co-Authors: Gregory J Basura, Kwaku D. Nantwi, Harry G. GoshgarianAbstract:Abstract Cervical Spinal Cord Hemisection leads to a disruption of bulboSpinal innervation of phrenic motoneurons resulting in paralysis of the ipsilateral hemidiaphragm. We have previously demonstrated separate therapeutic roles for theophylline, and more recently serotonin (5-HT) as modulators to phrenic nerve motor recovery; mechanisms that likely occur via adenosine A1 and 5-HT2 receptors, respectively. The present study was designed to specifically determine if concurrent stimulation of 5-HT2 receptors may enhance motor recovery induced by theophylline alone. Adult female rats (250–350 g; n=7 per group) received a left cervical (C2) Hemisection that resulted in paralysis of the ipsilateral hemidiaphragm. Twenty-four hours later rats were given systemic theophylline (15 mg/kg, i.v.), resulting in burst recovery in the ipsilateral phrenic nerve. Theophylline-induced recovery was enhanced with the 5-HT2A/2C receptor agonist, (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI; 1.0 mg/kg). DOI-evoked augmentation of theophylline-induced recovery was attenuated following subsequent injection of the 5-HT2 receptor antagonist, ketanserin (2.0 mg/kg). In a separate group, rats were pretreated with ketanserin, which did not prevent subsequent theophylline-induced respiratory recovery. However, pretreatment with ketanserin did prevent DOI-induced augmentation of the theophylline-evoked phrenic nerve burst recovery. Lastly, using immunocytochemistry and in situ hybridization, we showed for the first time a positive co-localization of adenosine A1 receptor mRNA and immunoreactivity with phrenic motoneurons of the cervical ventral horns. Taken together, the results of the present study suggest that theophylline may induce motor recovery likely at adenosine A1 receptors located at the level of the Spinal Cord, and the concurrent stimulation of converging 5-HT2 receptors may augment the response.
Xiao Ming Xu - One of the best experts on this subject based on the ideXlab platform.
-
early profiles of axonal growth and astroglial response after Spinal Cord Hemisection and implantation of schwann cell seeded guidance channels in adult rats
Journal of Neuroscience Research, 2005Co-Authors: Xiao Ming XuAbstract:We previously demonstrated that transplantation of Schwann cell-seeded channels promoted the regrowth of injured axons in the adult Spinal Cord. It is not clear, however, whether injured axons recapitulate the developmental scenarios to accomplish regeneration. In the present study, we investigated the early events associated with axonal regrowth after Spinal Cord Hemisection at the eighth thoracic level and implantation of a Schwann cell-seeded minichannel in adult rats. Animals were sacrificed at postoperative days (PO) 2, 4, 7, and 14. Anterograde tracing with fluoro-ruby showed that regenerating axons grew into the graft prior to PO2 and reached the distal end of the channel at PO7. These axons expressed both embryonic neural cell adhesion molecule (E-NCAM) and growth associated protein-43 (GAP-43). Although the expression of E-NCAM decreased by PO7, that of GAP-43 remained high throughout the first 2 weeks after implantation. A close relation of vimentin-positive astroglia to the growing axons in the host tissue suggested a contact-mediated role of these cells in axon guidance. Aggregation of glial fibrillary acidic protein (GFAP)-positive astrocytes together with the increased expression of chondroitin sulfate proteoglycans (CSPGs) starting at PO7 appeared to inhibit axonal growth at the host–graft interface. Thus, adult regenerating axons and astroglia do express developmentally related molecules that may facilitate axonal growth into a permissive graft at the early phase of injury and regeneration. These results suggest that molecules and astroglia essential to development are both important in influencing axonal regrowth in the adult Spinal Cord. © 2005 Wiley-Liss, Inc.
-
identification of regenerative tissue cables using in vivo mri after Spinal Cord Hemisection and schwann cell bridging transplantation
Journal of Neurotrauma, 2002Co-Authors: Christopher Iannotti, Huayin Li, Mark Stemmler, William H Perman, Xiao Ming XuAbstract:The purpose of this study was to examine the feasibility of a non-invasive in vivo magnetic resonance imaging (MRI) procedure, performed at 1.5 T, to detect regenerative tissue cables in a rat Spinal Cord Hemisection and Schwann cell (SC) bridging transplantation paradigm. Two months after implantation of a SC-seeded guidance channel (1.25 mm in diameter and 3.0 mm in length) into a T8 Spinal Cord Hemisection-gap lesion, axial fast-spin echo (FSE) T2-weighted MR imaging (T2WI) was performed. Axial T2WI through the graft identified a circular area of low intensity surrounded by high-intensity signal within the guidance channel lumen. Correlative histological assessments of Toluidine blue-stained sections confirmed that the low-intensity signal represented a tissue cable, which, in most cases, contained a substantial number of myelinated axons oriented along the rostro-caudal axis of the Spinal Cord. The percentage of guidance channel cross-sectional area occupied by the tissue cable, expressed as the tissu...
Georg W Kreutzberg - One of the best experts on this subject based on the ideXlab platform.
-
transient decrease of acetylcholinesterase in ventral horn neurons caudal to a low thoracic Spinal Cord Hemisection in the adult rat
Brain Research, 1996Co-Authors: W Nacimiento, Bernd Schlozer, Gary A Brook, L Toth, Rudolf Topper, J Noth, Georg W KreutzbergAbstract:Abstract Light microscopic enzyme: histochemistry was employed to study the alterations of acetylcholinesterase (AChE) within lumbosacral ventral horn neurons at survival times of 1, 4, 7, 14, 28, 60, and 90 days after low thoracic Spinal Cord Hemisection in adult rats. The intensity of histochemical staining was quantified using densitometric techniques. Virtually all ventral horn neurons of sham-operated and unoperated animals, which served as controls, displayed intense AChE staining. Hemisection of the Spinal Cord induced a transient, ipsilateral decrease of AChE staining in most neuronal cell bodies and in the neuropil of lamina IX at all segmental levels caudal to the lesion. Quantitative analysis of representative segments revealed a reduction of AChE in the ventral horn during a postoperative (p.o.) period of 1 to 28 days followed by a phase of recovery over the next two months. AChE activity still remained slightly reduced, even at 90 days p.o. The transient decrease in ACNE is a well-known metabolic response of axotomized motoneurons. However, the observed changes of AChE reactivity in intact motoneurons ipsilateral and caudal to the Hemisection are presumably induced by the interruption of supraSpinal descending pathways. These metabolic changes may functionally affect the whole motor unit and be involved in the disturbances of motor function following Spinal Cord injury.
W Nacimiento - One of the best experts on this subject based on the ideXlab platform.
-
transient decrease of acetylcholinesterase in ventral horn neurons caudal to a low thoracic Spinal Cord Hemisection in the adult rat
Brain Research, 1996Co-Authors: W Nacimiento, Bernd Schlozer, Gary A Brook, L Toth, Rudolf Topper, J Noth, Georg W KreutzbergAbstract:Abstract Light microscopic enzyme: histochemistry was employed to study the alterations of acetylcholinesterase (AChE) within lumbosacral ventral horn neurons at survival times of 1, 4, 7, 14, 28, 60, and 90 days after low thoracic Spinal Cord Hemisection in adult rats. The intensity of histochemical staining was quantified using densitometric techniques. Virtually all ventral horn neurons of sham-operated and unoperated animals, which served as controls, displayed intense AChE staining. Hemisection of the Spinal Cord induced a transient, ipsilateral decrease of AChE staining in most neuronal cell bodies and in the neuropil of lamina IX at all segmental levels caudal to the lesion. Quantitative analysis of representative segments revealed a reduction of AChE in the ventral horn during a postoperative (p.o.) period of 1 to 28 days followed by a phase of recovery over the next two months. AChE activity still remained slightly reduced, even at 90 days p.o. The transient decrease in ACNE is a well-known metabolic response of axotomized motoneurons. However, the observed changes of AChE reactivity in intact motoneurons ipsilateral and caudal to the Hemisection are presumably induced by the interruption of supraSpinal descending pathways. These metabolic changes may functionally affect the whole motor unit and be involved in the disturbances of motor function following Spinal Cord injury.
-
recovery of locomotion after Spinal Cord Hemisection an x ray study of the cat hindlimb
Experimental Neurology, 1996Co-Authors: J P Kuhtzbuschbeck, A Boczekfuncke, A Mautes, W Nacimiento, C WeinhardtAbstract:Abstract Hemisection of the Spinal Cord in adult cats is a suitable model to study the mechanisms underlying recovery of motor functions. The initial paresis of the hindlimb is followed by a considerable improvement of locomotor functions of the affected hindlimb. Kinematic analyses of treadmill locomotion were performed from 10 days to 8 months after complete Hemisections (right side) of the Spinal Cord at the thoracolumbar level, using X-ray cinematography for precise measurements of the hindlimb joint angles. The footfall pattern and the electromyogram were reCorded. Motor control of both proximal and distal hindlimb joints improved substantially during the 1st postoperative month. However, persistent locomotor deficits were still present several months after Hemisection. They could be divided into three groups of symptoms: (1) The gait pattern was disturbed with regard to interlimb coordination. The stance-phase duration of the right hindlimb was shortened. (2) The flexor capacity of the affected hindlimb was reduced, resulting in a slow insufficient flexion of the hip, knee, and ankle during the swing phase. (3) The timing of the flexion–extension events was impaired. The onset of the E1-extension was delayed and the amplitude was reduced. Electromyographic patterns of muscle activity during locomotion of the lesioned side hindlimb differed from the contralateral hindlimb, which served as a control. The results indicate that in spite of a good short-term functional improvement there are long-term locomotor deficits present after Spinal Cord Hemisection.