Spinal cord injury and protection

doi:10.1016/S0196-0644(85)80064-0

Annals of Emergency Medicine

Volume 14, Issue 8, August 1985, Pages 816-821

https://doi.org/10.1016/S0196-0644(85)80064-0 Get rights and content

Subsequent to traumatic injury of the spinal cord, a series of pathophysiological events occurs in the injured tissue that leads to tissue destruction and paraplegia. These include hemorrhagic necrosis, ischemia, edema, inflammation, neuronophagia, loss of Ca²⁺ from the extracellular space, and loss of K⁺ from the intracellular space. In addition, there is trauma-initiated lipid peroxidation and hydrolysis in cellular membranes. Both lipid peroxidation and hydrolysis can damage cells directly; hydrolysis also results in the formation of the biologically active prostaglandins and leukotrienes (eicosanoids). The time course of membrane lipid alterations seen in studies of antioxidant interventions suggests that posttraumatic ischemia, edema, inflammation, and ionic fluxes are the result of extensive membrane peroxidative reactions and lipolysis that produce vasoactive and chemotactic eicosanoids. A diverse group of compounds has been shown to be effective in ameliorating spinal cord injury in experimental animals. These include the synthetic glucocorticoid methylprednisolone sodium succinate (MPSS); the antioxidants vitamin E, selenium, and dimethyl sulfoxide (DMSO); the opiate antagonist naloxone; and thyrotropin-releasing hormone (TRH). With the exception of TRH, all of these agents have demonstrable antioxidant and/or anti-lipid-hydrolysis properties. Thus the effectiveness of these substances may lie in their ability to quench membrane peroxidative reactions or to inhibit the release of fatty acids from membrane phospholipids, or both. Whatever the mode of action, early administration appears to be a requirement for maximum effectiveness.

References (39)

GriffithsIR
Spinal cord blood flow after acute experimental cord injury in dogs
J Neurol Sci
(1976)
KorehK et al.
Lipid antioxidant properties of naloxone in vitro
Biochem Biophys Res Comm
(1981)
BrackenMB et al.
Incidence of acute traumatic hospitalized spinal cord injury in the United States, 1970–1977
Am J Epidemiol
(1981)
MeansED et al.
The pathophysiology of acute spinal cord injury
DemediukP et al.
Membrane lipid changes in laminectomized and traumatized cat spinal cord
FreemanLW et al.
Experimental observations of concussion and contusion of the spinal cord
Ann Surg
(1953)
RivlinAS et al.
Regional spinal cord blood flow in rats after severe cord trauma
J Neurosurg
(1978)
SandlerAN et al.
Effect of acute spinal cord compression injury on regional spinal cord blood flow in primates
J Neurosurg
(1976)
SenterJH et al.
Loss of autoregulation and post-traumatic ischemia following experimental spinal cord trauma
J Neurosurg
(1979)
YoungW et al.
Effect of high-dose corticosteroid therapy on blood flow, evoked potentials and extracellular calcium in experimental spinal injury
J Neurosurg
(1982)

BinghamWH et al.

Blood flow in normal and injured monkey spinal cord

J Neurosurg

(1975)

KobrineAI et al.

Role of histamine in posttraumatic spinal cord hyperemia and the luxury perfusion syndrome

J Neurosurg

(1976)

KobrineAI et al.

Local spinal cord blood flow in experimental traumatic myelopathy

J Neurosurg

(1975)

GriffithsIR et al.

Spinal cord blood flow and conduction during experimental cord compression in normotensive and hypotensive dogs

J Neurosurg

(1979)

DemopoulosHB et al.

The free radical pathology and the microcirculation in the major central nervous system disorders

Acta Physiol Scand [Suppl]

(1980)

DemopoulosHB et al.

Further studies on free radical pathology in the major central nervous system disorders: Effect of very high doses of methylprednisolone on the functional outcome, morphology, and chemistry of experimental spinal cord impact injury

Can J Physiol Pharmacol

(1982)

MilvyP et al.

Paramagnetic species and radical products in cat spinal cord

Ann NY Acad Sci

(1973)

HalliwellB et al.

Oxygen toxicity, oxygen radicals, transition metals and disease

Biochem J

(1984)

SiesjoBK

Cerebral circulation and metabolism

J Neurosurg

(1984)

Cited by (74)

Upregulation of hemeoxygenase enzymes HO-1 and HO-2 following ischemia-reperfusion injury in connection with experimental cardiac arrest and cardiopulmonary resuscitation: Neuroprotective effects of methylene blue
2021, Progress in Brain Research
Citation Excerpt :
Numerous factors thus contribute to the deleterious secondary damage of the neuronal tissue following the primary insult. Other factors inducing cell death include neurotransmitters such as glutamate, oxidative stress, membrane phospholipids disruption, and lipid or protein peroxidation products (Anderson et al., 1985; Balentine, 1985; Hall and Braughler, 1986; Hall et al., 1992; Young, 1988). Activation of caspase dependent pathway is another cascade that plays a major role in neuronal cell death triggered following ischemic brain stroke (Chan, 2004; Oshitari et al., 2008; Yakovlev and Faden, 2001).
Oxidative stress plays an important role in neuronal injuries after cardiac arrest. Increased production of carbon monoxide (CO) by the enzyme hemeoxygenase (HO) in the brain is induced by the oxidative stress. HO is present in the CNS in two isoforms, namely the inducible HO-1 and the constitutive HO-2. Elevated levels of serum HO-1 occurs in cardiac arrest patients and upregulation of HO-1 in cardiac arrest is seen in the neurons. However, the role of HO-2 in cardiac arrest is not well known. In this review involvement of HO-1 and HO-2 enzymes in the porcine brain following cardiac arrest and resuscitation is discussed based on our own observations. In addition, neuroprotective role of methylene blue- an antioxidant dye on alterations in HO under in cardiac arrest is also presented. The biochemical findings of HO-1 and HO-2 enzymes using ELISA were further confirmed by immunocytochemical approach to localize selective regional alterations in cardiac arrest. Our observations are the first to show that cardiac arrest followed by successful cardiopulmonary resuscitation results in significant alteration in cerebral concentrations of HO-1 and HO-2 levels indicating a prominent role of CO in brain pathology and methylene blue during CPR followed by induced hypothermia leading to superior neuroprotection after return of spontaneous circulation (ROSC), not reported earlier.
Relation of selenium status to neuro-regeneration after traumatic spinal cord injury
2019, Journal of Trace Elements in Medicine and Biology
Citation Excerpt :
In particular, the Cu-/Zn-dependent superoxide dismutase (SOD1) decreases the oxidative stress and attenuates the MMP-9 mediated blood-brain barrier (BBB) disruption as shown in a rodent model of spinal cord injury (SCI) [14]. This is noteworthy, due to ischemic and damaged neuronal tissue being affected by lipid peroxidation of the cell membrane resulting in local edema and inflammation [15–18]. The group of selenocysteine (Sec)-containing selenoproteins contributes to protecting cells from oxidative damage, especially via the families of Se-dependent glutathione peroxidases (GPX) and thioredoxin reductases (TXNRD).
The trace element selenium (Se) is crucial for the biosynthesis of selenoproteins. Both neurodevelopment and the survival of neurons that are subject to stress depend on a regular selenoprotein biosynthesis and sufficient Se supply by selenoprotein P (SELENOP).
Neuro-regeneration after traumatic spinal cord injury (TSCI) is related to the Se status.
Single-centre prospective observational study.
Three groups of patients with comparable injuries were studied; vertebral fractures without neurological impairment (n = 10, group C), patients with TSCI showing no remission (n = 9, group G0), and patients with remission developing positive abbreviated injury score (AIS) conversion within 3 months (n = 10, group G1). Serum samples were available from different time points (upon admission, and after 4, 9 and 12 h, 1 and 3 days, 1 and 2 weeks, and 1, 2 and 3 months). Serum trace element concentrations were determined by total reflection X-ray fluorescence, SELENOP by ELISA, and further parameters by laboratory routine.
Serum Se and SELENOP concentrations were higher on admission in the remission group (G1) as compared to G0. During the first week, both parameters remained constant in C and G0, whereas they declined significantly in the remission group. Similarly, the concentration changes between admission and 24 h were most pronounced in this group of recovering patients (G1). Binary logistic regression analysis including the delta of Se and SELENOP within the first 24 h indicated an AUC of 90.0% (CI: 67.4%–100.0%) with regards to predicting the outcome after TSCI.
A Se deficit might constitute a risk factor for poor outcome after TSCI. A dynamic decline of serum Se and SELENOP concentrations after admission may reflect ongoing repair processes that are associated with higher odds for a positive clinical outcome.
Hyperbaric oxygen treatment in the experimental spinal cord injury model
2014, Spine Journal
Citation Excerpt :
The primary purpose of all experimental and clinical studies on traumatic spinal cord injury is to reduce secondary injury. Although the total number of pathologic mechanisms caused by SCIs is not precisely known, processes, such as nitric oxide (NO) accumulation, resulting from increases in both calcium and free radicals are mentioned [7,11–16]. Lipid peroxidation is considered to be the principal cause among them [17].
Spinal cord trauma is a major cause of mortality and morbidity. Although no known treatment for spinal cord injury exists, a limited number of effective treatment modalities and procedures are available that improve secondary injury. Hyperbaric oxygen (HBO) treatment has been used to assist in neurologic recovery after cranial injury or ischemic stroke.
To report the findings on the effectiveness of HBO treatment on rats with experimental traumatic spinal cord injury. Improvement was evaluated through motor strength assessment and nitrite level assay testing.
We randomly distributed 40 rats among 5 groups of 8 rats each: sham incurable trauma, induced trauma, HBO treatment begun at the 1st hour, HBO treatment begun at the 6th hour, and HBO treatment begun at the 24th hour.
The HBO treatment was administered to rats in three of the groups and conducted in two 90-minute sessions, under an absolute atmospheric pressure of 2.4 at 100% oxygen for 5 days. In the motor strength evaluations, all the rats were observed during the inclined plane test and clinical motor examination on the first, third, and fifth days. In addition, the nitrite levels of spinal cord tissues on the sixth day were also studied.
Results from the inclined plane levels and motor strength test from all the three groups undergoing HBO treatment were higher than those from Group 2. It was also determined that early HBO treatment resulted in higher recovery rates (groups 3 and 4). The highest levels were seen in the group in which the HBO treatments were started in the first hour (Group 3). It was noted that nitrite levels of rats in the group exposed to trauma increased, compared with the sham group, but increased levels also diminished after HBO treatments. Again, the greatest decrease in nitrite levels was evident in the group where the HBO treatment was started the earliest (Group 3).
Prompt HBO treatment after trauma significantly contributed to the clinical, histopathologic, and biochemical recovery of the rats.
How DMSO, a Widely Used Solvent, Affects Spinal Cord Injury
2008, Annals of Vascular Surgery
Citation Excerpt :
In addition, there is trauma-initiated lipid peroxidation and hydrolysis in cellular membranes. Both lipid peroxidation and hydrolysis can damage cells directly.27 Protection of the spinal cord from ischemic insult is an important issue in the surgical treatment of thoracoabdominal aortic aneurysms.
The aim of this experimental study was to investigate whether dimethylsulfoxide (DMSO) has protective effects on spinal cord ischemia-reperfusion (I/R) injury. New Zealand rabbits were enrolled in the study. In addition to the control group, the study group received 0.1 mL/kg DMSO prior to ischemia. Blood samples were taken to obtain nitrite–nitrate levels during the surgical procedure. After neurological evaluation at 24 hr of reperfusion, lumbar spinal cords were removed for electron microscopic evaluation and malondialdehyde and myeloperoxidase measurements. The mean Tarlov score of the DMSO group was higher than that of the control group. Electron microscopic examination was carried out with tissue samples at 24 hr of reperfusion. The DMSO group had better preservation with the electron microscopic scoring compared to the control group. Malondialdehyde and myeloperoxidase levels were decreased in the DMSO group compared to the control group. Nitrite–nitrate levels were also lower in the DMSO group compared to control at 5 and 30 min of reperfusion. This study demonstrates a considerable neuroprotective effect of DMSO on neurological, biochemical, and histopathological analyses during periods of spinal cord I/R injury in rabbits. Although there was a difference between the DMSO and control groups in all measured parameters in our study, this was not statistically significant. DMSO deserves further investigation related with spinal cord ischemia and reperfusion. We should also consider the effect of DMSO when we use it as a solvent or vehicle during experimental I/R models.
Management of the Acutely Neurologic Patient
2006, Clinical Techniques in Equine Practice
Assessment and stabilization of the acutely neurologic equine patient presents a diagnostic and therapeutic challenge. Depending on the etiology of the neurologic condition and severity of its manifestations, further injury may result to both the central nervous system and body as a whole. Interventions should be aimed at medical stabilization of concurrent conditions, localization and assessment of the neurologic lesion, timely and rational medical therapies, and support for the animal as a whole while treatment continues.
Neuroprotective effect of etomidate on functional recovery in experimental spinal cord injury
2006, International Journal of Developmental Neuroscience
Citation Excerpt :
Many pathological changes seen after spinal cord trauma are thus secondary to the initial impact and include edema, altered blood flow and changes in microvascular permeability (Tator and Fehlings, 1991). Previous studies showed that one of the most important factors precipitating posttraumatic degeneration in the spinal cord is oxygen free radical-induced lipid peroxidation (Anderson et al., 1985a, 1993; Hall, 1992, 1993). Pharmacological intervention in the acute phase of spinal cord injury aims to counteract secondary neurotoxic events or to interrupt the progression of this process.
Primary impact to the spinal cord causes rapid oxidative stress after injury. To protect neural tissue, it is important to prevent secondary pathophysiological mechanisms. Etomidate, a strong antiexcitotoxic agent, stimulates the gamma aminobutyric acid (GABA) receptors. The purpose of this study was to investigate neurobehavioral and histological recovery and to evaluate the biochemical responses to treatment of experimental spinal cord injury (SCI) in rats with etomidate or methylprednisolone (MP) or both etomidate and MP.
Seventy-two rats were randomly allocated into six groups: a control group (laminectomy alone), a trauma group (laminectomy + trauma), a methylprednisolone group (30 mg/kg MP), an etomidate group (2 mg/kg), a methylprednisolone and etomidate combined treatment group (30 mg/kg MP and 2 mg/kg etomidate) and a vehicle group. Six rats from each group were killed at the 24th hour after the injury. Malondialdehyde, glutathione, nitric oxide and xanthine oxidase levels were measured. Neurological functions of the remaining rats were recorded weekly. Six weeks after injury, all of those rats were killed for histopathological assesssment.
Etomidate treatment revealed similar neurobehavioral and histopathological recovery to MP treatment 6 weeks after injury. Combined treatment did not provide additional neuroprotection.
Etomidate treatment immediately after spinal cord injury has similar neuroprotection to MP. In spite of different neuroprotection mechanisms, combined treatment with MP and etomidate does not provide extra protection.

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: Presented at the 1985 UAEM/IRIEM Research Symposium in Orlando, Florida, February 7–8, 1985.

: The work was supported by the Veterans Administration and by NIH Research Grants NS-08291 and NS-10165 and Training Grant NS-07091.

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Special contributionSpinal cord injury and protection

J Neurol Sci

Biochem Biophys Res Comm

Incidence of acute traumatic hospitalized spinal cord injury in the United States, 1970–1977

Am J Epidemiol

The pathophysiology of acute spinal cord injury

Membrane lipid changes in laminectomized and traumatized cat spinal cord

Experimental observations of concussion and contusion of the spinal cord

Ann Surg

Regional spinal cord blood flow in rats after severe cord trauma

J Neurosurg

Effect of acute spinal cord compression injury on regional spinal cord blood flow in primates

J Neurosurg

Loss of autoregulation and post-traumatic ischemia following experimental spinal cord trauma

J Neurosurg

Effect of high-dose corticosteroid therapy on blood flow, evoked potentials and extracellular calcium in experimental spinal injury

J Neurosurg

Blood flow in normal and injured monkey spinal cord

J Neurosurg

Role of histamine in posttraumatic spinal cord hyperemia and the luxury perfusion syndrome

J Neurosurg

Local spinal cord blood flow in experimental traumatic myelopathy

J Neurosurg

Spinal cord blood flow and conduction during experimental cord compression in normotensive and hypotensive dogs

J Neurosurg

The free radical pathology and the microcirculation in the major central nervous system disorders

Acta Physiol Scand [Suppl]

Further studies on free radical pathology in the major central nervous system disorders: Effect of very high doses of methylprednisolone on the functional outcome, morphology, and chemistry of experimental spinal cord impact injury

Can J Physiol Pharmacol

Paramagnetic species and radical products in cat spinal cord

Ann NY Acad Sci

Oxygen toxicity, oxygen radicals, transition metals and disease

Biochem J

Cerebral circulation and metabolism

J Neurosurg

Special contribution
Spinal cord injury and protection