Effect of hyperglycemia on progressive paraparesis in a rat metastatic spinal tumor model: Laboratory investigation

Matthew J. McGirt, Beril Gok, Starane Shepherd, Joseph Noggle, Giannina L. Garcés Ambrossi, Ali Bydon, Ziya L. Gokaslan

Research output: Contribution to journalArticle

Abstract

Object. Hyperglycemia has been shown to potentiate ischemic injury of the spinal cord by quenching vasodilators and potentiating tissue acidosis and free radical production. Steroid-induced hyperglycemia is a common event in the surgical management of metastatic epidural spinal cord compression (MESCC). The goal in this study was to determine whether experimentally induced hyperglycemia accelerates neurological decline in an established animal model of MESCC. Methods. Sixteen Fischer 344 rats underwent a transabdominal approach for implantation of a CRL-1666 breast adenocarcinoma cell line within the vertebral body of L-6. After 72 hours of recovery from tumor implantation, the animals received intraperitoneal injections every 12 hours of either 2 g/kg dextrose in 5 ml 0.09% saline (hyperglycemia, 8 rats) or 5 ml 0.09% saline alone (normoglycemia, 8 rats). Weights were taken daily, and the hindlimb function was tested daily after tumor implantation by using the Basso-Beattie-Bresnahan (BBB) scale (score range 1-21). Animals were killed at time of paralysis (BBB Score <7), and the volume of epidural tumor growth within the spinal canal was measured. To determine the degree of hyperglycemia induced by this dextrose regimen, a surrogate group of 10 Fischer 344 rats underwent intraperitoneal injections of 2 g/kg dextrose (5 rats) or 0.09% saline (5 rats) every 12 hours, and serum glucose levels were assessed 1, 3, 6, 8, 10, and 12 hours after injections for 24 hours. Results. Dextrose versus saline injections resulted in elevated mean serum glucose at 3 (259 vs 103 μg/dl), 6 (219 vs 102 μg/dl), 8 (169 vs 102 μg/dl), and 10 hours (118 vs 99 μg/dl) after injection, returning to normal levels by 12 hours (96 vs 103 μg/dl) just prior to subsequent injection. All rats had normal hindlimb function for the first 8 days after tumor implantation. Hyperglycemic versus normoglycemic rats demonstrated a worsened median BBB score by postimplantation Day 9 (Score 20 vs 21, p = 0.023) through Day 16 (Score 8 vs 12, p = 0.047). Epidural tumor volume demonstrated a near-linear growth rate across both groups; however, hyperglycemic rats developed paralysis earlier (median 15.5 vs 17.5 days, p = 0.0035), with significantly less epidural tumor volume (2.75 ± 0.38 cm3 vs 4 ± 0.41 cm3, p <0.001) at time of paralysis. Conclusions. In a rat model of metastatic epidural spinal cord compression, rats maintained in a hyperglycemic state experienced accelerated time to paralysis. Also, less epidural tumor volume was required to cause paralysis in hyperglycemic rats. These results suggest that hyperglycemic states may contribute to decreased spinal cord tolerance to compression resulting from MESCC. Clinical studies evaluating the effect of aggressive glucose control in patients with MESCC may be warranted.

Original languageEnglish (US)
Pages (from-to)9-15
Number of pages7
JournalJournal of Neurosurgery: Spine
Volume10
Issue number1
DOIs
StatePublished - Jan 2009

Fingerprint

Paraparesis
Hyperglycemia
Epidural Neoplasms
Spinal Cord Compression
Paralysis
Glucose
Neoplasms
Tumor Burden
Injections
Inbred F344 Rats
Hindlimb
Intraperitoneal Injections
Spinal Canal
Growth
Acidosis
Serum
Vasodilator Agents
Spinal Cord Injuries
Free Radicals
Spinal Cord

Keywords

  • Glucose
  • Hyperglycemia
  • Metastatic spinal tumor
  • Rat

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery
  • Neurology

Cite this

Effect of hyperglycemia on progressive paraparesis in a rat metastatic spinal tumor model : Laboratory investigation. / McGirt, Matthew J.; Gok, Beril; Shepherd, Starane; Noggle, Joseph; Garcés Ambrossi, Giannina L.; Bydon, Ali; Gokaslan, Ziya L.

In: Journal of Neurosurgery: Spine, Vol. 10, No. 1, 01.2009, p. 9-15.

Research output: Contribution to journalArticle

McGirt, Matthew J. ; Gok, Beril ; Shepherd, Starane ; Noggle, Joseph ; Garcés Ambrossi, Giannina L. ; Bydon, Ali ; Gokaslan, Ziya L. / Effect of hyperglycemia on progressive paraparesis in a rat metastatic spinal tumor model : Laboratory investigation. In: Journal of Neurosurgery: Spine. 2009 ; Vol. 10, No. 1. pp. 9-15.
@article{7fe80f28f0a84fda905aaf4430a662b5,
title = "Effect of hyperglycemia on progressive paraparesis in a rat metastatic spinal tumor model: Laboratory investigation",
abstract = "Object. Hyperglycemia has been shown to potentiate ischemic injury of the spinal cord by quenching vasodilators and potentiating tissue acidosis and free radical production. Steroid-induced hyperglycemia is a common event in the surgical management of metastatic epidural spinal cord compression (MESCC). The goal in this study was to determine whether experimentally induced hyperglycemia accelerates neurological decline in an established animal model of MESCC. Methods. Sixteen Fischer 344 rats underwent a transabdominal approach for implantation of a CRL-1666 breast adenocarcinoma cell line within the vertebral body of L-6. After 72 hours of recovery from tumor implantation, the animals received intraperitoneal injections every 12 hours of either 2 g/kg dextrose in 5 ml 0.09{\%} saline (hyperglycemia, 8 rats) or 5 ml 0.09{\%} saline alone (normoglycemia, 8 rats). Weights were taken daily, and the hindlimb function was tested daily after tumor implantation by using the Basso-Beattie-Bresnahan (BBB) scale (score range 1-21). Animals were killed at time of paralysis (BBB Score <7), and the volume of epidural tumor growth within the spinal canal was measured. To determine the degree of hyperglycemia induced by this dextrose regimen, a surrogate group of 10 Fischer 344 rats underwent intraperitoneal injections of 2 g/kg dextrose (5 rats) or 0.09{\%} saline (5 rats) every 12 hours, and serum glucose levels were assessed 1, 3, 6, 8, 10, and 12 hours after injections for 24 hours. Results. Dextrose versus saline injections resulted in elevated mean serum glucose at 3 (259 vs 103 μg/dl), 6 (219 vs 102 μg/dl), 8 (169 vs 102 μg/dl), and 10 hours (118 vs 99 μg/dl) after injection, returning to normal levels by 12 hours (96 vs 103 μg/dl) just prior to subsequent injection. All rats had normal hindlimb function for the first 8 days after tumor implantation. Hyperglycemic versus normoglycemic rats demonstrated a worsened median BBB score by postimplantation Day 9 (Score 20 vs 21, p = 0.023) through Day 16 (Score 8 vs 12, p = 0.047). Epidural tumor volume demonstrated a near-linear growth rate across both groups; however, hyperglycemic rats developed paralysis earlier (median 15.5 vs 17.5 days, p = 0.0035), with significantly less epidural tumor volume (2.75 ± 0.38 cm3 vs 4 ± 0.41 cm3, p <0.001) at time of paralysis. Conclusions. In a rat model of metastatic epidural spinal cord compression, rats maintained in a hyperglycemic state experienced accelerated time to paralysis. Also, less epidural tumor volume was required to cause paralysis in hyperglycemic rats. These results suggest that hyperglycemic states may contribute to decreased spinal cord tolerance to compression resulting from MESCC. Clinical studies evaluating the effect of aggressive glucose control in patients with MESCC may be warranted.",
keywords = "Glucose, Hyperglycemia, Metastatic spinal tumor, Rat",
author = "McGirt, {Matthew J.} and Beril Gok and Starane Shepherd and Joseph Noggle and {Garc{\'e}s Ambrossi}, {Giannina L.} and Ali Bydon and Gokaslan, {Ziya L.}",
year = "2009",
month = "1",
doi = "10.3171/2008.10.SPI08333",
language = "English (US)",
volume = "10",
pages = "9--15",
journal = "Journal of Neurosurgery: Spine",
issn = "1547-5654",
publisher = "American Association of Neurological Surgeons",
number = "1",

}

TY - JOUR

T1 - Effect of hyperglycemia on progressive paraparesis in a rat metastatic spinal tumor model

T2 - Laboratory investigation

AU - McGirt, Matthew J.

AU - Gok, Beril

AU - Shepherd, Starane

AU - Noggle, Joseph

AU - Garcés Ambrossi, Giannina L.

AU - Bydon, Ali

AU - Gokaslan, Ziya L.

PY - 2009/1

Y1 - 2009/1

N2 - Object. Hyperglycemia has been shown to potentiate ischemic injury of the spinal cord by quenching vasodilators and potentiating tissue acidosis and free radical production. Steroid-induced hyperglycemia is a common event in the surgical management of metastatic epidural spinal cord compression (MESCC). The goal in this study was to determine whether experimentally induced hyperglycemia accelerates neurological decline in an established animal model of MESCC. Methods. Sixteen Fischer 344 rats underwent a transabdominal approach for implantation of a CRL-1666 breast adenocarcinoma cell line within the vertebral body of L-6. After 72 hours of recovery from tumor implantation, the animals received intraperitoneal injections every 12 hours of either 2 g/kg dextrose in 5 ml 0.09% saline (hyperglycemia, 8 rats) or 5 ml 0.09% saline alone (normoglycemia, 8 rats). Weights were taken daily, and the hindlimb function was tested daily after tumor implantation by using the Basso-Beattie-Bresnahan (BBB) scale (score range 1-21). Animals were killed at time of paralysis (BBB Score <7), and the volume of epidural tumor growth within the spinal canal was measured. To determine the degree of hyperglycemia induced by this dextrose regimen, a surrogate group of 10 Fischer 344 rats underwent intraperitoneal injections of 2 g/kg dextrose (5 rats) or 0.09% saline (5 rats) every 12 hours, and serum glucose levels were assessed 1, 3, 6, 8, 10, and 12 hours after injections for 24 hours. Results. Dextrose versus saline injections resulted in elevated mean serum glucose at 3 (259 vs 103 μg/dl), 6 (219 vs 102 μg/dl), 8 (169 vs 102 μg/dl), and 10 hours (118 vs 99 μg/dl) after injection, returning to normal levels by 12 hours (96 vs 103 μg/dl) just prior to subsequent injection. All rats had normal hindlimb function for the first 8 days after tumor implantation. Hyperglycemic versus normoglycemic rats demonstrated a worsened median BBB score by postimplantation Day 9 (Score 20 vs 21, p = 0.023) through Day 16 (Score 8 vs 12, p = 0.047). Epidural tumor volume demonstrated a near-linear growth rate across both groups; however, hyperglycemic rats developed paralysis earlier (median 15.5 vs 17.5 days, p = 0.0035), with significantly less epidural tumor volume (2.75 ± 0.38 cm3 vs 4 ± 0.41 cm3, p <0.001) at time of paralysis. Conclusions. In a rat model of metastatic epidural spinal cord compression, rats maintained in a hyperglycemic state experienced accelerated time to paralysis. Also, less epidural tumor volume was required to cause paralysis in hyperglycemic rats. These results suggest that hyperglycemic states may contribute to decreased spinal cord tolerance to compression resulting from MESCC. Clinical studies evaluating the effect of aggressive glucose control in patients with MESCC may be warranted.

AB - Object. Hyperglycemia has been shown to potentiate ischemic injury of the spinal cord by quenching vasodilators and potentiating tissue acidosis and free radical production. Steroid-induced hyperglycemia is a common event in the surgical management of metastatic epidural spinal cord compression (MESCC). The goal in this study was to determine whether experimentally induced hyperglycemia accelerates neurological decline in an established animal model of MESCC. Methods. Sixteen Fischer 344 rats underwent a transabdominal approach for implantation of a CRL-1666 breast adenocarcinoma cell line within the vertebral body of L-6. After 72 hours of recovery from tumor implantation, the animals received intraperitoneal injections every 12 hours of either 2 g/kg dextrose in 5 ml 0.09% saline (hyperglycemia, 8 rats) or 5 ml 0.09% saline alone (normoglycemia, 8 rats). Weights were taken daily, and the hindlimb function was tested daily after tumor implantation by using the Basso-Beattie-Bresnahan (BBB) scale (score range 1-21). Animals were killed at time of paralysis (BBB Score <7), and the volume of epidural tumor growth within the spinal canal was measured. To determine the degree of hyperglycemia induced by this dextrose regimen, a surrogate group of 10 Fischer 344 rats underwent intraperitoneal injections of 2 g/kg dextrose (5 rats) or 0.09% saline (5 rats) every 12 hours, and serum glucose levels were assessed 1, 3, 6, 8, 10, and 12 hours after injections for 24 hours. Results. Dextrose versus saline injections resulted in elevated mean serum glucose at 3 (259 vs 103 μg/dl), 6 (219 vs 102 μg/dl), 8 (169 vs 102 μg/dl), and 10 hours (118 vs 99 μg/dl) after injection, returning to normal levels by 12 hours (96 vs 103 μg/dl) just prior to subsequent injection. All rats had normal hindlimb function for the first 8 days after tumor implantation. Hyperglycemic versus normoglycemic rats demonstrated a worsened median BBB score by postimplantation Day 9 (Score 20 vs 21, p = 0.023) through Day 16 (Score 8 vs 12, p = 0.047). Epidural tumor volume demonstrated a near-linear growth rate across both groups; however, hyperglycemic rats developed paralysis earlier (median 15.5 vs 17.5 days, p = 0.0035), with significantly less epidural tumor volume (2.75 ± 0.38 cm3 vs 4 ± 0.41 cm3, p <0.001) at time of paralysis. Conclusions. In a rat model of metastatic epidural spinal cord compression, rats maintained in a hyperglycemic state experienced accelerated time to paralysis. Also, less epidural tumor volume was required to cause paralysis in hyperglycemic rats. These results suggest that hyperglycemic states may contribute to decreased spinal cord tolerance to compression resulting from MESCC. Clinical studies evaluating the effect of aggressive glucose control in patients with MESCC may be warranted.

KW - Glucose

KW - Hyperglycemia

KW - Metastatic spinal tumor

KW - Rat

UR - http://www.scopus.com/inward/record.url?scp=61549092513&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=61549092513&partnerID=8YFLogxK

U2 - 10.3171/2008.10.SPI08333

DO - 10.3171/2008.10.SPI08333

M3 - Article

C2 - 19119926

AN - SCOPUS:61549092513

VL - 10

SP - 9

EP - 15

JO - Journal of Neurosurgery: Spine

JF - Journal of Neurosurgery: Spine

SN - 1547-5654

IS - 1

ER -