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

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

doi:10.3171/2008.10.spi08333

Cited by 7 publications

(6 citation statements)

References 52 publications

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“…In a rat spinal tumor model, hyperglycemia shortened the time to paralysis; in addition, a lower epidural tumor volume was required to cause paralysis in hyperglycemic rats. 26 Human studies examining the association between hyperglycemia and outcomes after spinal injuries are mainly limited to retrospective analyses. One review from a registry at a level 1 trauma center in Australia found hyperglycemia (at the time of injury) to be associated with subsequent functional disability and suboptimal physical health status in patients with spine injuries.…”

Section: Journal Of Vascular Surgerymentioning

confidence: 99%

“…[18][19][20][21][22][23] Experimental data in animals suggest that hyperglycemia may play a deleterious role in the setting of spinal cord ischemic injury; however, prospective human studies are lacking. [24][25][26] The purpose of this study was to examine the association between lower extremity weakness (LEW) and the glucose levels of blood and cerebrospinal fluid (CSF) in patients undergoing multibranched endovascular aneurysm repair (MBEVAR) of pararenal aortic aneurysms (PRAAs) and TAAAs.…”

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confidence: 99%

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Lower extremity weakness is associated with elevated blood and cerebrospinal fluid glucose levels following multibranched endovascular aortic aneurysm repair

Hiramoto

Fernandez

Gasper

et al. 2017

Journal of Vascular Surgery

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Objective: Hyperglycemia is associated with worsened clinical outcomes after central nervous system injury. The purpose of this study was to examine the association between lower extremity weakness (LEW) and the glucose levels of blood and cerebrospinal fluid (CSF) in patients undergoing multibranched endovascular aneurysm repair (MBEVAR) of thoracoabdominal and pararenal aortic aneurysms. Methods: Blood and CSF samples were collected preoperatively, immediately after aneurysm repair, and on postoperative day 1 in 21 patients undergoing MBEVAR. Data on demographics, operative repair, complications, and outcomes were collected prospectively. Results: There were 21 patients who underwent successful MBEVAR. Two patients had pre-existing paraplegia from prior open aortic surgery and were excluded from the current analysis. The mean age was 73 6 8 years, and 15 of 19 (79%) were men. In the postoperative period, 7 of 19 (37%) patients developed LEW. This was temporary in 5 of 19 (26%) patients and permanent in 2 of 19 (11%) patients. The LEW group was older than the non-LEW group (77 6 6 vs 70 6 9 years, respectively; P ¼ .10), had a lower preoperative glomerular filtration rate (58.6 6 18.5 vs 71.4 6 23.5 mL/min per 1.73 m 2 ; P ¼ .24), and was more likely to be taking a statin (100% vs 67%, respectively; P ¼ .13), but these did not reach statistical significance. There was no significant difference in the prevalence of diabetes mellitus, hypertension, coronary artery disease, lung disease, or peripheral artery disease between the LEW and non-LEW groups. There was also no difference in operative time, blood loss, contrast material volume, or fluoroscopy times between the two groups. Preoperative blood and CSF glucose levels were similar in those with and without LEW. During the postoperative period, glucose values in the blood and CSF were significantly higher in those patients who developed LEW compared with those who did not develop LEW. In all patients with LEW, the elevation in the blood or CSF glucose level preceded the development of LEW. In a multivariable logistic regression model, CSF glucose concentration on postoperative day 1 was significantly and independently associated with the development of LEW (odds ratio, 2.30 [1.03-5.14] per 10 mg/dL increase in CSF glucose; P ¼ .04). Conclusions: Elevated blood glucose and CSF glucose levels are associated with postoperative LEW in patients undergoing MBEVAR. The protective effect of euglycemia deserves further study in patients at risk for spinal cord ischemia.

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Section: Journal Of Vascular Surgerymentioning

confidence: 99%

mentioning

confidence: 99%

Lower extremity weakness is associated with elevated blood and cerebrospinal fluid glucose levels following multibranched endovascular aortic aneurysm repair

Hiramoto

Fernandez

Gasper

et al. 2017

Journal of Vascular Surgery

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“…30 This model has been previously used to test numerous treatment modalities ranging from local chemotherapy to radiotherapy. 2,3,13,14,31 In the context of the current study, this model tests the safety of applying local hyperthermia to tumors abutting the highly sensitive neural tissues of the spine and great vessels.…”

Section: Discussionmentioning

confidence: 99%

“…31 Anesthetized rats were placed on sterile drapes, and the abdomen was shaved and disinfected with a povidone-iodine solution. A 3-cm midline incision centered between the iliac crests was made to the skin, following the procedure described by Mantha et al 30 to expose the underlying abdominal muscles.…”

Section: Tumor Implantationmentioning

confidence: 99%

Characterization of intratumor magnetic nanoparticle distribution and heating in a rat model of metastatic spine disease

Zadnik¹,

Molina²,

Sarabia-Estrada³

et al. 2014

SPI

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Object The goal of this study was to optimize local delivery of magnetic nanoparticles in a rat model of metastatic breast cancer in the spine for tumor hyperthermia while minimizing systemic exposure. Methods A syngeneic mammary adenocarcinoma was implanted into the L-6 vertebral body of 69 female Fischer rats. Suspensions of 100-nm starch-coated iron oxide magnetic nanoparticles (micromod Partikeltechnologie GmbH) were injected into tumors 9 or 13 days after implantation. For nanoparticle distribution studies, tissues were harvested from a cohort of 36 rats, and inductively coupled plasma mass spectrometry and histopathological studies with Prussian blue staining were used to analyze the samples. Intratumor heating was tested in 4 anesthetized animals with a 20-minute exposure to an alternating magnetic field (AMF) at a frequency of 150 kHz and an amplitude of 48 kA/m or 63.3 kA/m. Intratumor and rectal temperatures were measured, and functional assessments of AMF-exposed animals and histopathological studies of heated tumor samples were examined. Rectal temperatures alone were tested in a cohort of 29 rats during AMF exposure with or without nanoparticle administration. Animal studies were completed in accordance with the protocols of the University Animal Care and Use Committee. Results Nanoparticles remained within the tumor mass within 3 hours of injection and migrated into the bone at 6, 12, and 24 hours. Subarachnoid accumulation of nanoparticles was noted at 48 hours. No evidence of lymphoreticular nanoparticle exposure was found on histological investigation or via inductively coupled plasma mass spectrometry. The mean intratumor temperatures were 43.2°C and 40.6°C on exposure to 63.3 kA/m and 48 kA/m, respectively, with histological evidence of necrosis. All animals were ambulatory at 24 hours after treatment with no evidence of neurological dysfunction. Conclusions Locally delivered magnetic nanoparticles activated by an AMF can generate hyperthermia in spinal tumors without accumulating in the lymphoreticular system and without damaging the spinal cord, thereby limiting neurological dysfunction and minimizing systemic exposure. Magnetic nanoparticle hyperthermia may be a viable option for palliative therapy of spinal tumors.

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“…19,20,29,35,37 One group studying cerebral ischemia in rats found that hyperglycemia reduced cerebral plasma volume, cerebral blood flow, and blood-brain barrier transport. 20 Another study investigating the effects of glucose levels following traumatic brain injury found that acute but not delayed hyperglycemia increased the contusion area and elevated neutrophil accumulation in the area of the cortical contusion.…”

Section: Discussionmentioning

confidence: 99%

Hyperglycemia is independently associated with post-operative function loss in patients with primary eloquent glioblastoma

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Woodworth

Chaichana

et al. 2012

Journal of Clinical Neuroscience

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The poor prognosis for patients with glioblastoma (GB) heightens the importance of maintaining function throughout treatment. Hyperglycemia has been linked to poor neurological outcomes following stroke, traumatic brain and spinal cord injury. We hypothesized this may also be true following the resection of GB. We assessed associations with post-operative function with the goal of identifying modifiable factors in the peri-operative period with a particular focus on blood glucose levels. Independent associations with worse post-operative function included: patient age, pre-operative motor deficit, deep tumor location, post-operative motor deficit, and elevated mean peri-operative glucose. Interestingly, controlling for associated factors including dexamethasone dosing, patients with elevated peri-operative glucose levels were nearly twice as likely to have new post-operative neurological deficits. These results suggest, together with the broad literature supporting a role for hyperglycemia in neurological injury, that this may represent a modifiable factor in the peri-operative care of these patients.

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

Cited by 7 publications

References 52 publications

Lower extremity weakness is associated with elevated blood and cerebrospinal fluid glucose levels following multibranched endovascular aortic aneurysm repair

Lower extremity weakness is associated with elevated blood and cerebrospinal fluid glucose levels following multibranched endovascular aortic aneurysm repair

Characterization of intratumor magnetic nanoparticle distribution and heating in a rat model of metastatic spine disease

Hyperglycemia is independently associated with post-operative function loss in patients with primary eloquent glioblastoma

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