Perfusion imaging of spinal cord contusion: injury-induced blockade and partial reversal by β2-agonist treatment in rats

2014 ◽  
Vol 20 (2) ◽  
pp. 164-171 ◽  
Author(s):  
Abraham Brown ◽  
Anna Nabel ◽  
William Oh ◽  
Joseph D. Etlinger ◽  
Richard J. Zeman
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Perfusion Imaging ◽  
Laser Doppler ◽  
Tissue Loss ◽  
Partial Recovery ◽  
Locomotor Function ◽  
Adrenoceptor Agonist ◽  
Cord Injury ◽  
Contusion Injury

Object Traumatic injury to the spinal cord results in considerable delayed tissue loss. The authors investigated the extent to which ischemia occurs following contusion-induced spinal cord injury and whether ischemia exacerbates tissue damage that leads to the loss of locomotor function. They also determined if ischemia is reversed with β2–adrenoceptor agonist treatment, which has been established to be neuroprotective following contusion injury. Methods The extent and role of circulation loss in spinal cord injury was determined in an established experimental model of contusion injury. The spinal cord dura mater of Wistar rats was exposed by performing a laminectomy at T-8 to T-11. Laser Doppler perfusion imaging was then used to measure microcirculation in the exposed spinal cord. After imaging, a moderately severe contusion injury was produced using a weight-drop device unto the exposed dura at T-10. Perfusion imaging was again performed, scans were quantitated, and integrated intensities were compared. Results Postinjury imaging revealed an 18%–27% reduction in perfusion in regions rostral and caudal to the injury site, and a 68% reduction was observed at the contusion epicenter. These perfusion losses persisted for at least 48 hours. At 24 hours after injury, some rats were intraperitoneally injected with 2 mg/kg of the β2–adrenoceptor agonist clenbuterol, which has been shown to promote the partial recovery of locomotor function and spare spinal cord tissue when administered within 2 days after contusion injury. Clenbuterol injection caused a gradual increase in perfusion, which was detectable at 30 minutes postinjection and continued over time, resulting in an 127% overall increase in perfusion at the epicenter 24 hours after treatment. Conclusions These results suggest that the occurrence of chronic perfusion loss after contusion contributes to delayed damage and tissue loss. In contrast, β2–adrenoceptor agonist treatment may exert neuroprotection by restoring perfusion, thereby preventing ischemic neurodegeneration. The ability of laser Doppler imaging to measure the loss of perfusion and its restoration upon treatment suggests that it may have clinical utility in the assessment and treatment of spinal cord injury.

STEREOTACTIC RADIOSURGERY IMPROVES LOCOMOTOR RECOVERY AFTER SPINAL CORD INJURY IN RATS

Neurosurgery ◽  
2008 ◽  
Vol 63 (5) ◽  
pp. 981-988 ◽  
Author(s):  
Richard J. Zeman ◽  
Xialing Wen ◽  
Nengtai Ouyang ◽  
Ronald Rocchio ◽  
Lynn Shih ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stereotactic Radiosurgery ◽  
Spinal Cord Tissue ◽  
Injured Spinal Cord ◽  
Locomotor Recovery ◽  
Locomotor Function ◽  
Cord Injury ◽  
Contusion Injury ◽  
X Irradiation

Abstract OBJECTIVE Currently, because of the precision of stereotactic radiosurgery, radiation can now be delivered by techniques that shape the radiation beam to the tissue target for a variety of clinical applications. This avoids unnecessary and potentially damaging irradiation of surrounding tissues inherent in conventional irradiation, so that irradiation of the minimum volume of tissue necessary for optimal therapeutic benefit can be achieved. Although conventional x-irradiation has been shown to improve recovery from spinal cord injury in animals, the efficacy of targeted irradiation of the injured spinal cord has not been demonstrated previously. The purpose of these studies was to determine whether stereotactic x-irradiation of the injured spinal cord can enhance locomotor function and spare spinal cord tissue after contusion injury in a standard experimental model of spinal cord injury. METHODS Contusion injury was produced in rats at the level of T10 with a weight-drop device, and doses of x-irradiation were delivered 2 hours after injury via a Novalis, 6-MeV linear accelerator shaped beam radiosurgery system (BrainLAB USA, Westchester, IL) in 4 sequential fractions, with beam angles 60 to 70 degrees apart, at a rate of 6.4 Gy/minute. The target volume was a 4 × 15-mm cylinder along the axis of the spinal cord, with the isocenter positioned at the contusion epicenter. Locomotor function was determined for 6 weeks after injury with the 21-point Basso, Beattie, and Bresnahan (BBB) locomotor scale and tissue sparing in histological sections of the spinal cord. RESULTS Locomotor function recovered progressively during the 6-week postinjury observation period. BBB scores were significantly greater in the 10-Gy x-irradiated group compared with controls (9.4 versus 7.3; P < 0.05), indicating hind limb weight support or dorsal stepping in contrast to hind limb joint mobility without weight bearing. Doses in the range of 2 to 10 Gy increased BBB scores progressively, whereas greater doses of 15 to 25 Gy were associated with lower BBB scores. The extent of locomotor recovery after treatment with x-irradiation correlated with measurements of spared spinal cord tissue at the contusion epicenter. CONCLUSION These results suggest a beneficial role for stereotactic radiosurgery in a rat model of acute spinal cord contusion injury and raise hopes for human treatment strategies. Additional animal studies are needed to further define potential benefits.

81. Tempol, an antioxidant, improves locomotor function and decreases tissue loss after spinal cord injury in the rat

2004 ◽  
Vol 4 (5) ◽  
pp. S42-S43
Author(s):  
Virany Hillard ◽  
Richard Zeman ◽  
Kaushik Das ◽  
Yan Zhang ◽  
Hong Peng ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Tissue Loss ◽  
Locomotor Function ◽  
Cord Injury

scholarly journals Selective inhibition of ASIC1a confers functional and morphological neuroprotection following traumatic spinal cord injury

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1822 ◽  
Author(s):  
Liam M. Koehn ◽  
Qing Dong ◽  
Sing-Yan Er ◽  
Lachlan D. Rash ◽  
Glenn F. King ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Barrier Function ◽  
Hind Limb ◽  
Tissue Loss ◽  
Functional Improvement ◽  
Spinal Cord Tissue ◽  
Post Injury ◽  
Locomotor Function ◽  
Cord Injury

Tissue loss after spinal trauma is biphasic, with initial mechanical/haemorrhagic damage at the time of impact being followed by gradual secondary expansion into adjacent, previously unaffected tissue. Limiting the extent of this secondary expansion of tissue damage has the potential to preserve greater residual spinal cord function in patients. The acute tissue hypoxia resulting from spinal cord injury (SCI) activates acid-sensing ion channel 1a (ASIC1a). We surmised that antagonism of this channel should provide neuroprotection and functional preservation after SCI. We show that systemic administration of the spider-venom peptide PcTx1, a selective inhibitor of ASIC1a, improves locomotor function in adult Sprague Dawley rats after thoracic SCI. The degree of functional improvement correlated with the degree of tissue preservation in descending white matter tracts involved in hind limb locomotor function. Transcriptomic analysis suggests that PcTx1-induced preservation of spinal cord tissue does not result from a reduction in apoptosis, with no evidence of down-regulation of key genes involved in either the intrinsic or extrinsic apoptotic pathways. We also demonstrate that trauma-induced disruption of blood-spinal cord barrier function persists for at least 4 days post-injury for compounds up to 10 kDa in size, whereas barrier function is restored for larger molecules within a few hours. This temporary loss of barrier function provides a “treatment window” through which systemically administered drugs have unrestricted access to spinal tissue in and around the sites of trauma. Taken together, our data provide evidence to support the use of ASIC1a inhibitors as a therapeutic treatment for SCI. This study also emphasizes the importance of objectively grading the functional severity of initial injuries (even when using standardized impacts) and we describe a simple scoring system based on hind limb function that could be adopted in future studies.

scholarly journals Selective inhibition of ASIC1a confers functional and morphological neuroprotection following traumatic spinal cord injury

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1822 ◽  
Author(s):  
Liam M. Koehn ◽  
Natassya M. Noor ◽  
Qing Dong ◽  
Sing-Yan Er ◽  
Lachlan D. Rash ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Barrier Function ◽  
Hind Limb ◽  
Tissue Loss ◽  
Functional Improvement ◽  
Spinal Cord Tissue ◽  
Post Injury ◽  
Locomotor Function ◽  
Cord Injury

Tissue loss after spinal trauma is biphasic, with initial mechanical/haemorrhagic damage at the time of impact being followed by gradual secondary expansion into adjacent, previously unaffected tissue. Limiting the extent of this secondary expansion of tissue damage has the potential to preserve greater residual spinal cord function in patients. The acute tissue hypoxia resulting from spinal cord injury (SCI) activates acid-sensing ion channel 1a (ASIC1a). We surmised that antagonism of this channel should provide neuroprotection and functional preservation after SCI. We show that systemic administration of the spider-venom peptide PcTx1, a selective inhibitor of ASIC1a, improves locomotor function in adult Sprague Dawley rats after thoracic SCI. The degree of functional improvement correlated with the degree of tissue preservation in descending white matter tracts involved in hind limb locomotor function. Transcriptomic analysis suggests that PcTx1-induced preservation of spinal cord tissue does not result from a reduction in apoptosis, with no evidence of down-regulation of key genes involved in either the intrinsic or extrinsic apoptotic pathways. We also demonstrate that trauma-induced disruption of blood-spinal cord barrier function persists for at least 4 days post-injury for compounds up to 10 kDa in size, whereas barrier function is restored for larger molecules within a few hours. This temporary loss of barrier function provides a “treatment window” through which systemically administered drugs have unrestricted access to spinal tissue in and around the sites of trauma. Taken together, our data provide evidence to support the use of ASIC1a inhibitors as a therapeutic treatment for SCI. This study also emphasizes the importance of objectively grading the functional severity of initial injuries (even when using standardized impacts) and we describe a simple scoring system based on hind limb function that could be adopted in future studies.

Drastic Decrease in Isoflurane Minimum Alveolar Concentration and Limb Movement Forces after Thoracic Spinal Cooling and Chronic Spinal Transection in Rats

2005 ◽  
Vol 102 (3) ◽  
pp. 624-632 ◽  
Author(s):  
Steven L. Jinks ◽  
Carmen L. Dominguez ◽  
Joseph F. Antognini
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Minimum Alveolar Concentration ◽  
Tail Flick ◽  
Noxious Stimulation ◽  
Partial Recovery ◽  
Spinal Transection ◽  
Thoracic Spinal ◽  
Cord Injury ◽  
Stimulation Of

Background Individuals with spinal cord injury may undergo multiple surgical procedures; however, it is not clear how spinal cord injury affects anesthetic requirements and movement force under anesthesia during both acute and chronic stages of the injury. Methods The authors determined the isoflurane minimum alveolar concentration (MAC) necessary to block movement in response to supramaximal noxious stimulation, as well as tail-flick and hind paw withdrawal latencies, before and up to 28 days after thoracic spinal transection. Tail-flick and hind paw withdrawal latencies were measured in the awake state to test for the presence of spinal shock or hyperreflexia. The authors measured limb forces elicited by noxious mechanical stimulation of a paw or the tail at 28 days after transection. Limb force experiments were also conducted in other animals that received a reversible spinal conduction block by cooling the spinal cord at the level of the eighth thoracic vertebra. Results A large decrease in MAC (to </= 40% of pretransection values) occurred after spinal transection, with partial recovery (to approximately 60% of control) at 14-28 days after transection. Awake tail-flick and hind paw withdrawal latencies were facilitated or unchanged, whereas reflex latencies under isoflurane were depressed or absent. However, at 80-90% of MAC, noxious stimulation of the hind paw elicited ipsilateral limb withdrawals in all animals. Hind limb forces were reduced (by >/= 90%) in both chronic and acute cold-block spinal animals. Conclusions The immobilizing potency of isoflurane increases substantially after spinal transection, despite the absence of a baseline motor depression, or "spinal shock." Therefore, isoflurane MAC is determined by a spinal depressant action, possibly counteracted by a supraspinal facilitatory action. The partial recovery in MAC at later time points suggests that neuronal plasticity after spinal cord injury influences anesthetic requirements.

Slope analysis of somatosensory evoked potentials in spinal cord injury for detecting contusion injury and focal demyelination

2010 ◽  
Vol 17 (9) ◽  
pp. 1159-1164 ◽  
Author(s):  
Gracee Agrawal ◽  
David Sherman ◽  
Anil Maybhate ◽  
Michael Gorelik ◽  
Douglas A. Kerr ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Evoked Potentials ◽  
Somatosensory Evoked Potentials ◽  
Slope Analysis ◽  
Cord Injury ◽  
Contusion Injury ◽  
Focal Demyelination

Genetic Ablation of Transcription Repressor Bach1 Reduces Neural Tissue Damage and Improves Locomotor Function after Spinal Cord Injury in Mice

2009 ◽  
Vol 26 (1) ◽  
pp. 31-39 ◽  
Author(s):  
Haruo Kanno ◽  
Hiroshi Ozawa ◽  
Yoshihiro Dohi ◽  
Akira Sekiguchi ◽  
Kazuhiko Igarashi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Tissue Damage ◽  
Neural Tissue ◽  
Locomotor Function ◽  
Genetic Ablation ◽  
Cord Injury

Ultrastructural scoring of graded acute spinal cord injury in the rat

2002 ◽  
Vol 97 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Erkan Kaptanoglu ◽  
Selcuk Palaoglu ◽  
H. Selcuk Surucu ◽  
Mutlu Hayran ◽  
Etem Beskonakli
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Behavioral Assessment ◽  
Traumatic Injury ◽  
Significant Negative Correlation ◽  
Content Type ◽  
Cord Injury ◽  
Contusion Injury ◽  
Weight Drop ◽  
Fine Print

Object. There is a need for an accurate quantitative histological technique that also provides information on neurons, axons, vascular endothelium, and subcellular organelles after spinal cord injury (SCI). In this paper the authors describe an objective, quantifiable technique for determining the severity of SCI. The usefulness of ultrastructural scoring of acute SCI was assessed in a rat model of contusion injury. Methods. Spinal cords underwent acute contusion injury by using varying weights to produce graded SCI. Adult Wistar rats were divided into five groups. In the first group control animals underwent laminectomy only, after which nontraumatized spinal cord samples were obtained 8 hours postsurgery. The weight-drop technique was used to produce 10-, 25-, 50-, and 100-g/cm injuries. Spinal cord samples were also obtained in the different trauma groups 8 hours after injury. Behavioral assessment and ultrastructural evaluation were performed in all groups. When the intensity of the traumatic injury was increased, behavioral responses showed a decreasing trend. A similar significant negative correlation was observed between trauma-related intensity and ultrastructural scores. Conclusions. In the present study the authors characterize quantitative ultrastructural scoring of SCI in the acute, early postinjury period. Analysis of these results suggests that this method is useful in evaluating the degree of trauma and the effectiveness of pharmacotherapy in neuroprotection studies.

scholarly journals Effects of a Contusive Spinal Cord Injury on Spinal Motor Neuron Activity and Conduction Time in Rats

2020 ◽  
Author(s):  
Jordan A. Borrell ◽  
Dora Krizsan-Agbas ◽  
Randolph J. Nudo ◽  
Shawn B. Frost
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spike Activity ◽  
Short Latency ◽  
Neuron Activity ◽  
Emg Activity ◽  
Conduction Time ◽  
Dorsal Midline ◽  
Cord Injury ◽  
Contusion Injury

AbstractObjectiveThe purpose of this study was to determine the effects of spinal cord injury (SCI) on spike activity evoked in the hindlimb spinal cord of the rat from cortical electrical stimulation.ApproachAdult, male, Sprague Dawley rats were randomly assigned to a Healthy or SCI group. SCI rats were given a 175 kDyn dorsal midline contusion injury at the level of the T8 vertebrae. At four weeks post-SCI, intracortical microstimulation (ICMS) was delivered at several sites in the hindlimb motor cortex of anesthetized rats, and evoked neural activity was recorded from corresponding sites throughout the dorsoventral depths of the spinal cord and EMG activity from hindlimb muscles.Main resultsIn healthy rats, post-ICMS spike histograms showed reliable, evoked spike activity during a short-latency epoch 10-12 ms after the initiation of the ICMS pulse train (short). Longer latency spikes occurred between ~20-60 ms, generally following a Gaussian distribution, rising above baseline at time LON, followed by a peak response (Lp), and then falling below baseline at time LOFF. EMG responses occurred between LON and Lp (25-27 ms). In SCI rats, short-latency responses were still present, long-latency responses were disrupted or eliminated, and EMG responses were never evoked. The retention of the short-latency responses indicates that spared descending spinal fibers, most likely via the cortico-reticulospinal pathway, can still depolarize spinal cord motor neurons after a dorsal midline contusion injury.SignificanceThis study provides novel insights into the role of alternate pathways for voluntary control of hindlimb movements after SCI that disrupts the corticospinal tract in the rat.

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