scholarly journals Glial-Neuronal Interactions in Pathogenesis and Treatment of Spinal Cord Injury

Author(s):  
Nadezda Lukacova ◽  
Alexandra Kisucka ◽  
Katarina Kiss Bimbova ◽  
Maria Bacova ◽  
Maria Ileninova ◽  
...  

Traumatic spinal cord injury (SCI) elicits an acute inflammatory response which comprises numerous cell populations. It is driven by the immediate response of macro-phages and reactive M1 microglia, which triggers activation of genes responsible for the dysregulated microenvironment within the lesion site and in the spinal cord parenchyma immediately adjacent to the lesion. Recently published data indicate that microglia induces astrocyte activation and determines the fate of astrocytes. Conversely, astrocytes have the potency to trigger microglial activation and control their cellular functions. Here we review current information about the release of diverse signaling molecules (pro-inflammatory vs anti-inflammatory) in individual cell phenotypes (microglia, astrocytes, blood inflammatory cells) in acute and subacute SCI stages, and how they contribute to delayed neuronal death in a the surrounding spinal cord tissue which is spared and functional but reactive. In addition, temporal correlation in progressive degeneration of neurons and astrocytes and their functional interactions after SCI are discussed. Finally, the review highlight the time-dependent transformation of reactive mi-croglia (M1) and astrocytes (A1) into their neuroprotective phenotypes (M2a, M2c and A2) which are crucial for spontaneous post-SCI locomotor recovery. We also provide sug-gestions on how to increase functional outcome after SCI and discuss key therapeutic approaches.

2021 ◽  
Vol 22 (24) ◽  
pp. 13577
Author(s):  
Nadezda Lukacova ◽  
Alexandra Kisucka ◽  
Katarina Kiss Bimbova ◽  
Maria Bacova ◽  
Maria Ileninova ◽  
...  

Traumatic spinal cord injury (SCI) elicits an acute inflammatory response which comprises numerous cell populations. It is driven by the immediate response of macrophages and microglia, which triggers activation of genes responsible for the dysregulated microenvironment within the lesion site and in the spinal cord parenchyma immediately adjacent to the lesion. Recently published data indicate that microglia induces astrocyte activation and determines the fate of astrocytes. Conversely, astrocytes have the potency to trigger microglial activation and control their cellular functions. Here we review current information about the release of diverse signaling molecules (pro-inflammatory vs. anti-inflammatory) in individual cell phenotypes (microglia, astrocytes, blood inflammatory cells) in acute and subacute SCI stages, and how they contribute to delayed neuronal death in the surrounding spinal cord tissue which is spared and functional but reactive. In addition, temporal correlation in progressive degeneration of neurons and astrocytes and their functional interactions after SCI are discussed. Finally, the review highlights the time-dependent transformation of reactive microglia and astrocytes into their neuroprotective phenotypes (M2a, M2c and A2) which are crucial for spontaneous post-SCI locomotor recovery. We also provide suggestions on how to modulate the inflammation and discuss key therapeutic approaches leading to better functional outcome after SCI.


2007 ◽  
Vol 6 (4) ◽  
pp. 337-343 ◽  
Author(s):  
Virany H. Hillard ◽  
Hong Peng ◽  
Kaushik Das ◽  
Raj Murali ◽  
Chitti R. Moorthy ◽  
...  

Object Hyperbaric oxygen (HBO), the nitroxide antioxidant tempol, and x-irradiation have been used to promote locomotor recovery in experimental models of spinal cord injury. The authors used x-irradiation of the injury site together with either HBO or tempol to determine whether combined therapy offers greater benefit to rats. Methods Contusion injury was produced with a weight-drop device in rats at the T-10 level, and recovery was determined using the 21-point Basso-Beattie-Bresnahan (BBB) locomotor scale. Locomotor function recovered progressively during the 6-week postinjury observation period and was significantly greater after x-irradiation (20 Gy) of the injury site or treatment with tempol (275 mg/kg intraperitoneally) than in untreated rats (final BBB Scores 10.6 [x-irradiation treated] and 9.1 [tempol treated] compared with 6.4 [untreated], p < 0.05). Recovery was not significantly improved by HBO (2 atm for 1 hour [BBB Score 8.2, p > 0.05]). Interestingly, the improved recovery of locomotor function after x-irradiation, in contrast with antiproliferative radiotherapy for neoplasia, was inhibited when used together with either HBO or tempol (BBB Scores 8.2 and 8.3, respectively). The ability of tempol to block enhanced locomotor recovery by x-irradiation was accompanied by prevention of alopecia at the irradiation site. The extent of locomotor recovery following treatment with tempol, HBO, and x-irradiation correlated with measurements of spared spinal cord tissue at the contusion epicenter. Conclusions These results suggest that these treatments, when used alone, can activate neuroprotective mechanisms but, in combination, may result in neurotoxicity.


Neurosurgery ◽  
2008 ◽  
Vol 63 (5) ◽  
pp. 981-988 ◽  
Author(s):  
Richard J. Zeman ◽  
Xialing Wen ◽  
Nengtai Ouyang ◽  
Ronald Rocchio ◽  
Lynn Shih ◽  
...  

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 &lt; 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.


2006 ◽  
Vol 23 (5) ◽  
pp. 660-673 ◽  
Author(s):  
Jason R. Potas ◽  
Yu Zheng ◽  
Charbel Moussa ◽  
Melinda Venn ◽  
Catherine A. Gorrie ◽  
...  

Author(s):  
Andrew C. Smith ◽  
Denise R. O’Dell ◽  
Wesley A. Thornton ◽  
David Dungan ◽  
Eli Robinson ◽  
...  

Background: Using magnetic resonance imaging (MRI), widths of ventral tissue bridges demonstrated significant predictive relationships with future pinprick sensory scores, and widths of dorsal tissue bridges demonstrated significant predictive relationships with future light touch sensory scores, following spinal cord injury (SCI). These studies involved smaller participant numbers, and external validation of their findings is warranted. Objectives: The purpose of this study was to validate these previous findings using a larger independent data set. Methods: Widths of ventral and dorsal tissue bridges were quantified using MRI in persons post cervical level SCI (average 3.7 weeks post injury), and pinprick and light touch sensory scores were acquired at discharge from inpatient rehabilitation (average 14.3 weeks post injury). Pearson product-moments were calculated and linear regression models were created from these data. Results: Wider ventral tissue bridges were significantly correlated with pinprick scores (r = 0.31, p &lt; 0.001, N = 136) and wider dorsal tissue bridges were significantly correlated with light touch scores (r = 0.31, p &lt; 0.001, N = 136) at discharge from inpatient rehabilitation. Conclusion: This retrospective study’s results provide external validation of previous findings, using a larger sample size. Following SCI, ventral tissue bridges hold significant predictive relationships with future pinprick sensory scores and dorsal tissue bridges hold significant predictive relationships with future light touch sensory scores.


Author(s):  
Johannie Audet ◽  
Charly G. Lecomte

Tonic or phasic electrical epidural stimulation of the lumbosacral region of the spinal cord facilitates locomotion and standing in a variety of preclinical models with severe spinal cord injury. However, the mechanisms of epidural electrical stimulation that facilitate sensorimotor functions remain largely unknown. This review aims to address how epidural electrical stimulation interacts with spinal sensorimotor circuits and discusses the limitations that currently restrict the clinical implementation of this promising therapeutic approach.


2014 ◽  
Vol 1549 ◽  
pp. 1-10 ◽  
Author(s):  
H. Nait Taleb Ali ◽  
M.P. Morel ◽  
M. Doulazmi ◽  
S. Scotto-Lomassese ◽  
P. Gaspar ◽  
...  

2018 ◽  
Vol 28 (7) ◽  
pp. 2565-2566
Author(s):  
Daniela Popova ◽  
Mariela Filipova

Spinal stroke is a disease that is rare in neurological practice. Affects young people, mostly at the age of 30 years [2]. It may be ischemic or haemorrhagic. Etiological, ischemic spinal stroke is caused by atherosclerosis of the aorta and blood vessels of the spinal cord, muscle spasm, vasculitis, pregnancy, hemangioma or hernia [3, 4]. Hemorrhagic stroke is caused by dysplasia, tumors and blood diseases involving increased bleeding [1]. Spinal infarction most commonly develops in the basal spinal artery pool, which is responsible for the blood supply of the anterior 2/3 of the spinal cord tissue. Often, the disease starts with a sudden back pain with an enigmatic nature (in the area of the thoracic segment - Th 8), a gradually occurring weakness in the limbs and hypestesia, pelvic-tangle disorders [5]. The gait is very difficult to impossible.Purpose of the study: To test neurological tests in patients with spinal ischemic spinal cord injury. Assess their accessibility and reliability.


2022 ◽  
Vol 17 (6) ◽  
pp. 1318
Author(s):  
Jin-Zhu Bai ◽  
Yi-Xin Wang ◽  
Zhen Lyu ◽  
Guang-Hao Zhang ◽  
Xiao-Lin Huo

Sign in / Sign up

Export Citation Format

Share Document