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Comparison of medical complications following nontraumatic and traumatic spinal cord injury.

BACKGROUND: Nontraumatic spinal cord injury (NT/SCI) has been shown to represent a significant proportion of individuals admitted for SCI rehabilitation. Although medical complications of patients with traumatic SCI (T/SCI) have been well studied, there is a paucity of literature regarding those with nontraumatic SCI. Our objective was to compare the incidence of secondary SCI medical complications in patients with nontraumatic and traumatic SCI. DESIGN: A 2-year prospective data comparison of 117 patients with SCI admitted to a regional SCI rehabilitation unit and tertiary university medical center was undertaken. NT/SCI was defined as spinal stenosis, tumorous compression, vascular ischemia, and infectious etiologies. METHODS: Outcome measures included secondary SCI medical complications, injury characteristics, demographics, and rehabilitation outcomes. Statistical analyses were conducted between the 38 NT/SCI and 79 T/SCI who met admission criteria for acute inpatient rehabilitation. RESULTS: Statistically significant differences (P<.05) between nontraumatic and traumatic SCI were noted for deep venous thrombosis (7.9% vs 22.8%), pressure ulcers (21.1% vs 41.8%), autonomic dysreflexia (0% vs 24.1%), pneumonia (2.6% vs 26.6%), orthostatic hypotension (5.3% vs 36.7%), spasticity (21.1% vs 44.3%), and wound infections (16% vs 3%). Similar incidences were found for depression (23.7% vs 26.6%), urinary tract infections (52.6% vs 67.1%), heterotopic ossification (2.6% vs 7.6%), pain at admission (55.3% vs 62.0%), and gastrointestinal bleed (2.6% vs 2.5%). In addition, significant differences were noted between NT/SCI and T/SCI for age (55 years vs 39 years), rehabilitation length of stay (26.4 days vs 43.0 days), and neurologically complete injury (5.3% vs 45.6%). CONCLUSION: This study indicates that patients with NT/SCI present with different incidences of secondary SCI medical complications when compared with individuals with T/SCI. These data, along with differences in demographics, clinical presentation, and rehabilitation outcomes, have important implications for the medical, rehabilitation management, and long-term outcome of individuals with NT/SCI.

Adult↗

Aberrant reflexes and function of the pelvic organs following spinal cord injury in man.

Spinal cord injuries can be devastating on quality of life and lost opportunities due to their impact on bladder, bowel and sexual functions. Supra-sacral spinal lesions can cause incontinence by interrupting those pathways, which normally coordinate the bladder, bowel and sphincters. From a scientific perspective, neural control of the pelvic organs is one of the most intriguing in the body, involving both somatic and autonomic pathways participating in an exquisitely fine integration of lumbo-sacral reflexes. This review details the interactions of somatic and autonomic lumbo-sacral pathways responsible for coordinating the bladder and sphincters, the nature of their aberration post-injury and those aspects of neural control of the pelvic organs that are amenable to neurophysiological examination in man. It will focus in greater detail on how measurement of pelvic floor and sphincter reflexes can be used to assess the modulatory effects of sacral autonomic pathways on sacral somatic reflexes and vice versa including the so called "guarding reflex" and vesical inhibitory reflexes. The effects of volitional modulation of these reflexes will be discussed in relation to people with both complete and incomplete lesions. Finally the possible utility of such neurophysiological measures for complementing the established neurological classification and the assessment of somatic sensory-motor impairment in spinal cord injury will be discussed.

Animals↗

Morphological changes in sympathetic preganglionic neurons after spinal cord injury in rats.

Spinal cord injury results in abnormal sympathetic control of the cardiovascular system, perhaps because of reactions of sympathetic preganglionic neurons to loss of their supraspinal afferent inputs. We investigated morphological changes in sympathetic preganglionic neurons in rats one week after midthoracic spinal cord hemisection or complete transection and one month after complete transection. Morphological changes in adrenal sympathetic preganglionic neurons retrogradely-labelled by cholera toxin were examined as well as changes in other thoracic preganglionic neurons identified by their expression of reduced nicotinamide adenine dinucleotide phosphate-diaphorase. Reactive astrogliosis around these neurons was determined by assessing changes in immunoreactivity to glial fibrillary acidic protein. Changes in immunoreactivity to the synaptic vesicular protein synaptophysin were also evaluated in these areas. One week after transection, a comparison of sympathetic preganglionic neurons rostral and caudal to the lesion revealed significant loss of dendrites and decreased cell size caudal to the injury. Reactive astrocytes surrounded sympathetic preganglionic neurons as far as six segments below the transection. Constitutive expression of synaptophysin was observed rostral to the cord hemisection and synaptophysin expression was increased caudal to the lesion by seven days after the injury. One month after transection, the dendritic arbor of preganglionic neurons was re-established and the intensity of the reactive gliosis around the preganglionic neurons was diminished throughout the thoracic cord. These findings demonstrate that sympathetic preganglionic neurons undergo significant atrophy within a week after deafferentation and that this reaction is reversed within one month. Reactive astrogliosis could contribute to plastic changes in the neuropil that affect the sympathetic neurons, and the enhanced expression of synaptophysin in the gray matter caudal to a cord injury is consistent with fibre outgrowth leading to new synapse formation. Such re-organization could be one of the mechanisms for disorders in blood pressure control that occur after spinal cord injury.

Animals↗

Neurological recovery distal to the zone of injury in 172 cases of closed, traumatic spinal cord injury.

The Southwest Regional System for Treatment of Spinal Cord Injury (Good Samaritan Hospital and St Joseph's Hospital, Phoenix, Arizona) treated 325 cases of traumatic spinal cord injury during the period June 1970 through December 1975. Of these, 172 met the study population criteria of the cases reported by Frankel et al. (1969) in their paper 'The value of postural reduction in the initial management of closed injuries of the spine with paraplegia and tetraplegia'. These cases are compared with those reported by Frankel et al. (1969). Cases were divided into neurological categories. The demography of the two study populations was amazingly similar as was the neurological results. The means for the reported neurological changes show that the average recovery for patients treated at Stoke Mandeville was slightly greater for each neurological category; however, this difference was statistically significant only for cervical cases (P less than 0.01). One of the differences in the treatment given by the two centres was that the Southwest Regional System performed surgery on 39% of its cases and Stoke Mandeville none. The Southwest Regional System's non-operated cervical cases showed less average neurological recovery than Stoke Mandeville cervical cases (P less than 0.001). Comparison between the Southwest Regional System non-operated cases and operated cases revealed no significant differences within any neurological category. The average neurological change reported by both centres was relatively small, documenting that from the onset of injury the majority of people sustaining spinal cord injury are committed to living with paralysis, in most cases severe, for the rest of their lives.

Arizona↗

Demyelination and remyelination after spinal cord injury.

Since the discovery in the 1960s that remyelination can occur in the damaged central nervous system (CNS) (Bunge et al. 1961), there has been much progress in understanding the cellular and molecular biology of oligodendroglia and the factors that regulate their propagation, migration, differentiation, maturation, and ability to myelinate nerve axons. More recently, greater understanding of disease states and the role of oligodendrocytes in remyelination have sparked tremendous interest in this once obscure field. Although the explosion of information is being hampered by adherence to commonly held beliefs based on empirical evidence, novel molecular and cellular tools are allowing scientists to address age-old assumptions. It is now recognized that, as well as promoting salutatory conduction along axons, oligodendroglia are important near-term clinical targets for restoring function after CNS injury, particularly spinal cord injury. Thus, remyelination appears to be one of the most feasible restoration strategies. This review focuses on concepts that are important for developing strategies of repair. The brightest young scientists will be attracted into this exciting field by its near-term potential for human application.

Animals↗

Effects of methylprednisolone and MK-801 on functional recovery after experimental chronic spinal cord injury.

STUDY DESIGN: An experimental study was conducted to evaluate the effects of methylprednisolone and MK-801 after the compressive injury of spinal cord in rats. OBJECTIVES: To investigate the effect of methylprednisolone and non-competitive NMDA antagonist MK-801 in long-term functional outcome after spinal cord injury (SCI). METHODS: A randomized group A of Sprague-Dawley rats were treated with MK-801 (1.0 mg/kg, n=10; Group A) after a compression injury. A group of methylprednisolone (MP)-treated (30 mg/kg, n=10; Group B) and non-treated animals (n=9; Group C) were included for comparison. The functional motor outcome such as inclined plane (IP), toe spreading reflex (TSR), and modified Tarlov scale (TS) were measured in each animal at regular time points up to 8 weeks post-treatment. Histologically the injury site was scored in four groups and immunohistochemically Wallerian Degeneration (WD), astrocytosis and expression of beta-amyloid protein was identified. RESULTS: In examining the IP data, no significant difference was recognized between the group means (P-value>0.5). For the TSR, there were no differences in the group responses. For the TS, the differences were not statistically significant. Only group B showed significance in cavitation scores compared to group A (P>0.0094), WD was significantly different than group C (P>0.03), astrocytosis was significantly higher than group A (P>0.001) and modest presence of beta-amyloid protein. CONCLUSION: Our data indicate that one time bolus administration of MK-801 lacks any significant effect on axonal function in chronically injured rats. Daily bolus administration of MP at 30 mg/kg also did not ensure a better functional outcome. Immunohistochemically we have been able to show significant differences in WD, astrocytosis and small insignificant changes in beta-amyloid protein.

Amyloid beta-Peptides↗

Delayed diaphragm recovery in 12 patients after high cervical spinal cord injury. A retrospective review of the diaphragm status of 107 patients ventilated after acute spinal cord injury.

STUDY DESIGN: The functional outcome of the diaphragm after acute spinal cord injury was reviewed over a 16 year period for 107 patients who had required assisted ventilation in the acute phase. OBJECTIVES: To quantify the incidence of recovery of diaphragm function which occurred beyond the period of acute oedema; to produce a time-related profile of this as a guide to clinicians considering phrenic nerve pacing; and to assess the value of phrenic nerve testing in predicting recovery. SETTING: The Southport Regional Spinal Injuries Centre, Southport, England. METHODS: Bilateral phrenic nerve and diaphragm integrity was assessed clinically, by spirometry, and by fluoroscopy without and with phrenic nerve stimulation. RESULTS: Thirty-one per cent of all the ventilated patients (33 cases), with a level of injury between C1 and C4 (Scale A in ASIA Impairment Scale), had diaphragmatic paralysis at the time of respiratory failure. The subsequent diaphragm recovery which appeared in seven of these patients, between 40 and 393 days (mean 143), permitted weaning from ventilatory support at 93 to 430 days (mean 246) after the acute injury, with a vital capacity of over 15 ml kg(-1) at that stage. The diaphragm recovery in a further five patients, whose vital capacity remained below 10 ml kg(-1) and who could not be fully weaned, occurred significantly later, between 84 and 569 days (mean 290), P=0.053. Negative phrenic nerve tests were followed by weaning at a later interval in several cases. By contrast, one patient with an early positive phrenic stimulation test and subsequent diaphragm activity could not be weaned from the ventilator. CONCLUSION: Twenty-one per cent of the patients with initial diaphragm paralysis were ultimately able to breathe independently after 4 and 14 months, whilst a further 15% had some diaphragm recovery. Phrenic nerve testing should be repeated at 3 monthly intervals for the first year after high tetraplegia.

Acute Disease↗

Tactile unit properties after human cervical spinal cord injury.

Properties of tactile afferent units innervating the glabrous skin of the hand were examined by microneurography in 11 individuals who had no or impaired touch perception due to chronic (> 1 year post-injury) cervical spinal cord injury (SCI). The results were compared with published control data. The adaptation properties [fast adaptation unit (FA) or slow adaptation unit (SA)], the indentation force threshold, and the size of the receptive field of each unit were assessed using calibrated von Frey hairs. Units were classified as type I (FAI, SAI) or type II (FAII, SAII) if the receptive field was small and well defined or large and diffuse, respectively. Sensitivity to skin stretch was also used to distinguish between the two slowly adapting unit types. In SCI subjects, 66 tactile afferents (and 16 unclassified muscle receptors) were sampled from all the glabrous skin areas typically innervated by the median nerve. Each unit type was represented in similar proportions in the SCI and control data. Similarly, there was an increase in the innervation density from the palm to the finger tips in SCI subjects, as found in control subjects. Afferent axon conduction velocities were not different for the SCI and control data. Indentation force thresholds and receptive field sizes of each unit type were also similar with one exception. The receptive fields for FAII units were larger after SCI. However, when data from all unit types were pooled, receptive fields were larger and indentation force thresholds were higher in SCI subjects. This may be the consequence of the thin, smooth, soft and significantly more compliant glabrous skin of the SCI subjects, factors which may influence the transmission of force from the skin surface to the receptors. Twenty-four units showed sustained responses to passive bending of the fingers and usually an increase in firing rate during finger extension. Eight of these units were slowly adapting tactile units. The others were unclassified units located deep within the forearm. Morphological estimates indicated no loss of myelinated nerve fibres in the median nerve 6 months after SCI. Motor as well as sensory nerve fibres were therefore unaffected below the elbow. Thus, tactile units were largely intact after chronic human cervical SCI despite changes in the mechanical transmission in the skin, and perception deficit.

Adult↗

A study on client selection criteria and services for home health care--C.V.A., head and spinal cord injury in patients.

This study was done to clarify the types of health care that should be offered. It focus on developing client selection criteria based on the needs of inpatients with cerebral vascular diseases, head injuries and spinal cord injuries. Two research methods were adopted. One was a methodological approach for developing client selection criteria and the other was analytical approach to clarify the types of services to be offered. From the research findings, the following summarized conclusions have been drawn. 1. The problem and item criteria used to select patients requiring home health care, namely, a prototype evaluation tool, consisted of 12 items in four areas; physiological status, functional status, psychological status and environmental status. After assessing each item at three levels, the categorization was done according to the classification criteria. The item internal consistency of the completed tool was .8358, .8390, the interrater reliability was in the range of 84 percent-98 percent and the classification consistency was 92 percent. As external criteria, the relationship of the prototype tool to the Health Status Scale, the Barthel Index of Functional Status Assessing Devices and the number of health problems of the patient was examined and all were found to be statistically significant, verifying the validity of the tool. 2. Using the tool to classify the inpatients according to the established client selection criteria, 84.2 percent were classified as patients requiring home health care, 8.8 percent were assessed as suitable for outpatient care and 7.0 percent were assessed as patients needing to be hospitalized. 3. Clients assessed as requiring home health care had 72 different kinds of health problems, which could be classified into four categories; 54 types of physiological status problems, 8, psychological, 6, functional and 4, environmental status problems. For each problem, the percentage of patients who suffered from the disorders ranged from 2.1 percent-66 percent. More than half of the subjects had problems related to urination, paralysis, contracture or locomotion. For the physiological category, many of the health problems were due to disorders of muscles and bone, whereas skin and breathing disorders were relatively low. The mean number of health problems in this category as 11.1. 4. Reviewing the literature, it was found that home health care consisted of 10 activity areas, namely, sanitation, nutrition, breathing, skin, body temperature maintenance, medication, assessment and observation, education and counselling.(ABSTRACT TRUNCATED AT 400 WORDS)

Cerebrovascular Disorders↗

Neurochemical plasticity and the role of neurotrophic factors in bladder reflex pathways after spinal cord injury.

Transection of the spinal cord that interrupts the spinobulbospinal micturition reflex pathway, abolishes voluntary voiding and initially produces an areflexic bladder with complete urinary retention. However, depending upon the species, reflex bladder activity slowly recovers over the course of weeks or months. In chronic spinal animals, reflex mechanisms in the lumbosacral spinal cord are capable of duplicating many of the functions performed by reflex pathways in animals with an intact spinal cord and can induce bladder hyperreflexia. However, the bladder does not empty efficiently due to a loss of bladder-sphincter coordination (bladder-sphincter dyssynergia). In contrast to normal animals in which the sphincter relaxes during voiding, animals with a spinal cord injury exhibit sphincter contractions during voiding, an increase in urethral outlet resistance, urinary retention, bladder hyperreflexia, bladder overdistension, and an increase in bladder afferent cell size. Changes in electrophysiological or neurochemical properties of bladder afferent cells in the dorsal root ganglia and of spinal pathways could contribute to the emergence of the spinal micturition reflex, bladder hyperreflexia and changes in the pharmacologic responses of reflex pathways in the lumbosacral spinal cord after spinal cord injury. Urinary bladder hyperreflexia after spinal cord injury may reflect a change in the balance of neuroactive compounds in bladder reflex pathways. This review will detail: (1) changes in the neurochemical phenotype of bladder afferent neurons and of spinal neurons mediating micturition reflexes after spinal cord injury, with an emphasis on three neuroactive compounds, neuronal nitric oxide synthase (nNOS), galanin, and pituitary adenylate cyclase activating polypeptide (PACAP); (2) possible functional consequences on bladder reflexes of changes in spinal cord neurochemistry after spinal cord injury, and (3) the potential role of neurotrophic factors expressed in the urinary bladder or spinal cord after spinal cord injury in mediating these neurochemical changes.

Afferent Pathways↗

Fatal injury surveillance report, Delaware, 1990. Head and spinal cord injuries.

The Delaware Disabilities Prevention Program is funded through a five-year Centers for Disease Control and Prevention (CDC) grant to prevent primary and secondary disabilities associated with mental retardation and low socioeconomic status; head and spinal cord injuries; and sickle cell disease. This report focuses on fatal head and spinal cord injuries. Death certificates and autopsy reports from 1990 were the data sources used for this study. In 1990, 122 fatal head injuries and 20 fatal spinal cord injuries occurred among Delaware residents. Eight of these individuals experienced both head and spinal cord injuries. Motor vehicle crashes caused the majority of both head and spinal cord deaths. Suicides, homicides, and falls were the other major causes of fatal head injuries. Deaths are only the tip of the injury iceberg. Head and spinal cord injuries can cause lifelong disabilities affecting family, friends, and the entire community.

Accidents, Traffic↗

Ischemic injury-specific gene expression in the rat spinal cord injury model using hypoxia-inducible system.

STUDY DESIGN: A spinal cord injury and in vitro neural hypoxia models were used to evaluate the hypoxia responsive gene expression. OBJECTIVES: To limit the risk of unwanted overexpression of therapeutic genes, we developed a hypoxia-inducible gene therapy system using the erythropoietin (Epo) enhancer and the RTP801 promoter. SUMMARY OF BACKGROUND DATA: Gene therapy is an emerging therapeutic technique to treat spinal cord injury. However, uncontrolled overexpression of therapeutic genes in nondisease tissues during gene therapy raises a doubt about its safety. Post-traumatic ischemia is an important factor worsening the spinal cord damage, and hypoxia could regulate the gene expressions using a hypoxia-inducible promoter. METHODS: The plasmids, pEpo-SV-Luc and pRTP801-Luc, were constructed. Mouse neuroblastoma cells (N2A) were used to evaluate the hypoxia-inducible gene expression in vitro.- Gene transfection and expression were allowed for 24 hours under normoxia (pO2, 152 mm Hg) or hypoxia (pO2, 7.6 mm Hg). Spinal cord injury was made using clip compression. Plasmids were injected directly into the injured spinal cord immediately following injury. The gene expression was assessed by luciferase assay. RESULTS: pEpo-SV-Luc and pRTP801-Luc showed more than three times higher gene expression in N2A cells under hypoxia than normoxia. The expression level of luciferase in the injured spinal cord was higher than in the normal spinal cord. Immunostaining demonstrated that neurons, astrocytes, and capillary endothelial cells expressed luciferase in the cytoplasm. CONCLUSIONS: The pEpo-SV-Luc and pRTP801-Luc systems are effective in that they induce gene expression specifically in neurons under the hypoxic condition and spinal cord injury.

Animals↗

Characteristics of injuries to the cervical spine and spinal cord in polytrauma patient population: experience from a regional trauma unit.

STUDY DESIGN: Retrospective analysis of a prospectively collected trauma database of a Level 1 (tertiary) trauma center. OBJECTIVE: To define the features of the cervical spinal injuries in polytrauma population admitted to the regional trauma unit. SETTING: Canada, Ontario Province, Toronto, Sunnybrook Health Sciences Center. METHODS: All trauma admissions between 1987 and 1996 entered prospectively into a trauma registry database were studied for incidence, demographic and epidemiological details of cervical spine (cord and column) injuries. RESULTS: A total of 468 patients (66% male) with cervical spinal injury (CSI) from 1198 spinal injuries admitted to the regional trauma center were identified. Seventy-five per cent of the CSI involved were aged less than 50 years; nearly 30% were in the third decade alone. Overall, the commonest spinal level injured was C2 (27%) followed by C5 (22%). Older population (above 60 years of age) had C1 + 2 involved more often than the young (P=0.02). Motor vehicular crashes (MVC) accounted for 71%, followed by pedestrian trauma (10%), sport injuries (7%). Spinal cord injury (SCI) was noted in 27%; complete in 16% and incomplete in 11% and more frequently at C4 or C5 level compared with C1, C2 (P<0.00001); the former level had more often a complete SCI (P=0.06). Though MVC produced 74% of SCI, only 27% had neurological deficits. Recreational trauma produced SCI in 45%, motor cycle crashes (MCC) in 37% and a rear passenger in MVC in 34% that was complete in 78%, 71% and 73% respectively. Front seat passenger and driver in MVC had a C5 level injury while a rear seat passenger had at C4 (P<0.001). The C1 level injury had high association with severe and life threatening head and neck and facial injuries compared with the more frequently injured spinal levels; either C2 (P=0.03) or C5 (P=0.004). Similarly C1 injuries had higher ISS compared with C2 (P<0.0001) and C5 (P<0.008). CONCLUSIONS: C2 was the commonest fractured spine while SCI was more frequent at C5. Older and pedestrian population had higher incidences of injuries at C1 and C2. Sport and MCC resulted in severe SCI. The level of spine injured was different between a front and a rear seat occupant in MVC.

Adult↗

Paediatric spinal trauma and associated injuries.

Paediatric spinal injuries, although rare (1-2% of all paediatric fractures) are associated with the highest mortality rate of all orthopaedic injuries in children. The low incidence is due, not only to the plasticity of the paediatric spine, but also the difficulty of diagnosis and the usually severe if not fatal associated injuries. A 10-year (1995-2004) retrospective study was undertaken of all patients treated for a spinal injury at our institute, which functions as both an acute care centre and a tertiary referral centre for seriously injured children. The study was performed in order to highlight the unique features of spinal injuries in children, and to assess the incidence and pattern of associated injuries. A total of 40 patients had a documented diagnosis of spinal injury. The charts and radiographs of all patients were retrieved and reviewed. The median age was 10 years (range 2-15) and 25 were male. The causative factors were motor vehicle accidents in 16, falls in 14, sport injuries in 7 and assaults in 3. Over 65% of the children sustained one or more associated injuries, the mean injury severity score was 18.95. There were two deaths, both in patients with severe multiple trauma and associated spinal fracture. Treatment included closed reduction in two patients and posterior open reduction and stabilisation in two patients, with one of these also requiring decompression. Spinal injuries in children differ from adults due primarily to the biomechanical and anatomical features of the developing musculoskeletal system. When a spinal injury is identified on initial radiographic or clinical evaluation of an injured child, one should have a high index of suspicion that concurrent, potentially life-threatening injuries may be present.

Accidental Falls↗

Behavioral and demographic predictors of suicide after traumatic spinal cord injury.

Among people with spinal cord injuries, death from suicide is two to six times more prevalent than in the general population. To determine if individual characteristics and behaviors present during rehabilitation can identify high-risk individuals, records of 5,200 spinal cord injured patients admitted to the Rocky Mountain Regional Spinal Injury System were reviewed. Of 489 deaths, 9% were due to suicide. They were compared with a control group of equal size, matched on age, gender, and injury level. The two groups differed significantly on postinjury despondency; expressions of shame, apathy, and hopelessness; and preinjury family disruption (p less than .01). They also differed on alcohol abuse, active involvement in the injury, preinjury depression or despondency, destructive behavior, and one aspect of etiology (p less than .05). Discriminant analysis yielded a predictive model that correctly classified 81% of the suicide group and 79% of the control group. Many of the demographic predictors identified in this study are similar to those reported in the scientific literature. However, when combined with specific behavioral characteristics manifested during rehabilitation, they comprise an array of variables that permits development of a clinical model for predicting suicide among persons with spinal cord injuries.

Adolescent↗

A possible role of RhoA/Rho-kinase in experimental spinal cord injury in rat.

Secondary injury following traumatic spinal cord injury is induced by the activation of a number of cellular and molecular changes. RhoA, a small GTPase, regulates the organization of the actin cytoskeleton, gene expression, cell proliferation, and has been implicated in the regenerative process. This study was undertaken to investigate the involvement of the RhoA signaling pathway in the secondary injury that follows traumatic spinal cord injury in rats. RhoA mRNA and protein expressions were enhanced significantly in the injured spinal cord 1 week after surgery (P<0.05, ANOVA). C3 exozyme (RhoA inhibitor), Y-27632 (selective Rho kinase inhibitor), and Fasudil (non-selective protein kinase inhibitor) were administered after spinal cord injury, and the subjects were evaluated for 5 weeks as per BBB locomotor score. Poor rat response interrupted the C3 experiment. Y-27632 slightly, but significantly (P<0.05, ANOVA), delayed the recovery. Fasudil significantly improved the BBB score (P<0.05, ANOVA). In conclusion, spinal cord injury activates the RhoA/Rho-kinase alpha, beta associated pathway. However, their role in secondary injury or in the improvement of functional recovery remains unclear. Fasudil might exert a cytoprotective effect by mechanisms other than inhibiting Rho-kinase alpha, beta.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗