Insulin administration protects from paraplegia in the rat aortic occlusion model

LeMay, Daniel R.; Lu, Alice; Zelenock, Gerald B.; DʼAlecy, Louis G.

doi:10.1016/0022-4804(88)90177-1

Cited by 31 publications

(11 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conversely, the administration of insulin, and the subsequent decrease in glycemia down to levels similar to those that we observed, not only prevented from aggravating spinal cord damage, but even resulted in neuroprotection when compared to not pretreated control animals. 30,34 In our Experiment 2, we also observed a relationship between fasting and blood gases. Either before or after injury, PaCO 2 and bicarbonates were significantly higher in not fasted rats.…”

Section: Methodssupporting

confidence: 58%

See 1 more Smart Citation

Role of Glycemia in Acute Spinal Cord Injury: Data from a Rat Experimental Model and Clinical Experience

Sala

Menna

Bricolo

et al. 1999

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

While experimental and clinical evidence indicates that in brain injury blood glucose increases with injury severity and hyperglycemia worsens neurological outcome, the role of blood glucose in secondary mechanisms of neuronal damage after acute spinal cord injury has not yet been investigated. Data from spinal cord ischemia models suggests a deleterious effect of hyperglycemia, likely due to enhanced lactic acidosis, which is primarily dependent on the amount of glucose available to be metabolized. The purpose of this study is to summarize preliminary experimental and clinical observations on the role of blood glucose in acute spinal cord injury. Between 1995 and 1996 we used the New York University (NYU) rat spinal cord injury model to test the following hypotheses: 1) Blood glucose levels increase with injury severity. 2) Fasting protects from hyperglycemia and prevents secondary damage to the spinal cord. 3) Postinjury-induced hyperglycemia (dextrose 5% 2 gm/Kg) enhances spinal lesion volume. From a clinical perspective, we reviewed blood glucose records of 47 patients admitted to the Department of Neurosrgery in Verona, between 1991 and 1995, within 24 hours of acute spinal cord injury in order to determine: a) the incidence of hyperglycemia (> 140 mg/dl); b) the correlation between blood glucose and injury severity; and c) the role of methylprednisolone in affecting blood glucose. Results indicate that in a graded spinal cord injury model: 1) Early after injury, more severe contusions support significantly higher blood glucose levels. 2) Fasting overnight does not directly affect spinal cord lesion volume but influences blood gases, and we observed that a slightly systemic acidosis plays a minor neuroprotective role. Fasting also ensures more consistent normoglycemic baseline blood glucose values. 3) Postinjury-induced moderate hyperglycemia (160-190 mg/dl) does not significantly affect spinal cord injury. In the clinical study, we observed that during the first 24 hours after spinal cord injury: a) Glycemia ranges between 90 and 243 mg/dl (mean value 143 mg/dl), and close to 50% of the patients present blood glucose values higher than normal. b) Methylprednisolone administration is not associated to significantly higher blood glucose levels. c) There is a trend for larger glucose rises with more severe injury.

show abstract

Section: Methodssupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Role of Glycemia in Acute Spinal Cord Injury: Data from a Rat Experimental Model and Clinical Experience

Sala

Menna

Bricolo

et al. 1999

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

show abstract

“…Our laboratory has performed a complementary study using insulin to prevent hyperglycemia in a rat model of spinal cord ischemia with the similar result that mild insulin-induced hypoglycemia appears to protect neurologic function. 29 There are several mechanisms by which insulin could be protective in the brain. Insulin decreases hepatic glycogenolysis and gluconeogenesis and lowers plasma glucose concentration by preferentially increasing uptake into muscle and fat and therefore reduces the amount of glucose circulating and available for brain metabolism.…”

mentioning

confidence: 99%

Insulin administration protects neurologic function in cerebral ischemia in rats.

LeMay

Gehua

Zelenock

et al. 1988

Stroke

114

View full text Add to dashboard Cite

Hyperglycemia exacerbates neurologic damage in clinical and experimental central nervous system ischemia. The purpose of our study was to determine if insulin administration before significantly alters neurologic deficit and survival after ischemia using a newly developed rat cerebral ischemia model. One hour before the onset of ischemia, 40 200-300 -g Sprague-Dawley rats received intraperitoneal injections of either 1 ml normal saline or 0.4, 0.5, or 0.6 units regular insulin in 1 ml normal saline. Rats were then intubated and ventilated with 1-1.5% halothane. The aortic arch was exposed, and snares were placed on the innominate, left carotid, and left subclavian arteries. A 20-minute occlusion was begun, and anesthesia was discontinued. Baseline plasma glucose concentration was similar (p=0.48, Student's t test) in both groups, but it subsequently was significantly lower in the 0.4 unit insulin-treated group up to 4 hours after occlusion (p<0.0035, Student's t test). Neurologic deficit was scored on a 50-point scale (0=normal, 50=severe deficit) 1, 4, 18, and 24 hours after occlusion. In the 0.4 unit insulin-treated group the neurologic deficit score was significantly lower than in the salinetreated group 1, 4, 18, and 24 hours after occlusion (p<0.005, Student's t test). Survival was significantly higher (p=0.001) in the 0.4 unit insulin-treated (1.7 unit/kg dose) group than in the saline-treated group. No rats died when preocclusion plasma glucose concentration was between 65 and 175 mg/dl. We conclude that insulin can be used to maintain plasma glucose concentration within a normoglycemic to mildly hypoglycemic range, which is associated with decreased behavioral neurologic deficit and increased survival following temporary cerebral ischemia. Hyperglycemia or more extreme hypoglycemia (glucose concentration less than approximately 65 mg/dl) is detrimental in this model. (Stroke 1988;19:1411-1419) H yperglycemia has been shown to exacerbate neurologic deficit in many experimental models of central nervous system (CNS) hypoxic-ischemic injury. -8 Clinical studies also indicate an adverse effect on outcome when CNS ischemia occurs in the setting of hyperglycemia. Diabetic patients experiencing a stroke have significantly worse outcomes than nondiabetic stroke patients. 9 Other studies have confirmed an increased mortality rate in acute stroke patients with fasting plasma glucose concentrations of >110 mg/dl. 10 These findings suggest that even relatively mild hyperglycemia, whether exogenously or endogenously induced, significantly worsens postischemic neurologic outcome. In the clinical setting, hyperglycemia resulting from exogenous glucose administration is potentially preventable but often inadvertently produced by administration of intravenous fluids. A more difficult problem arises in dealing with endogenous elevations of plasma glucose concentrations in patients at risk for ischemic neurologic injury. Examples include cardiac arrest patients and evolving stroke patients with concurrent hyperglycemia and...

show abstract

“…Experimental models of spinal cord ischemia have been developed in many animals, including dog 4 , rabbit 5 , baboon 6 , pig 7 , and rat 8 . In these models thoracic or abdominal aorta is cross-clamped, causing significant but incomplete reduction in spinal cord blood flow 9 .…”

Section: Introductionmentioning

confidence: 99%

Is subdiaphragmatic aortic cross-clamping a suitable model for spinal cord ischemia/reperfusion injury study in rats?

Carrillo¹,

Guimarães²,

Vasconcelos³

et al. 2006

Acta Cir. Bras.

View full text Add to dashboard Cite

show abstract

Insulin administration protects from paraplegia in the rat aortic occlusion model

Cited by 31 publications

References 20 publications

Role of Glycemia in Acute Spinal Cord Injury: Data from a Rat Experimental Model and Clinical Experience

Role of Glycemia in Acute Spinal Cord Injury: Data from a Rat Experimental Model and Clinical Experience

Insulin administration protects neurologic function in cerebral ischemia in rats.

Is subdiaphragmatic aortic cross-clamping a suitable model for spinal cord ischemia/reperfusion injury study in rats?

Contact Info

Product

Resources

About