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Effect of combination therapy using hypothermia and granulocyte colony-stimulating factor in a rat transient middle cerebral artery occlusion model.

Ghahari L, Safari M, Joghataei MT, Mehdizadeh M, Soleimani M - Iran. Biomed. J. (2014)

Bottom Line: Treatment with hypothermy plus G-CSF (2.69 ± 0.24%) could significantly reduce brain swelling volume than other treatment groups.Our major finding is that mild hypothermic treatment plus G-CSF significantly reduced mortality rate and edema and improved neurological function.The results suggest that the combination of hypothermia and G-CSF is more effectively than other treatment groups being used alone.

View Article: PubMed Central - PubMed

Affiliation: Dept. of Anatomy, Medical School, Iran University of Medical Science, Tehran, Iran. mansourehsoleimani@gmail.com.

ABSTRACT

Background: Stroke is the third leading cause of death. Hypothermia has been recognized as an effective method in reducing brain injury. In this study, we assessed the effects of granulocyte colony-stimulating factor (G-CSF) as a neuroprotective agent and mild hypothermia on mortality, behavioral function, infarct volume, and brain edema in Wistar rats.

Methods: Forty male rats were used in five groups (eight rats in each group): control, hypothermy, G-CSF, combination hypothermy + CSF, and sham. Rats were anesthetized by injection of chloral hydrate (400 mg/kg) intraperitoneally. Transient cerebral ischemia was induced by 60-min intraluminal occlusion of left middle cerebral artery. Hypothermia, initiated at the time of reperfusion and G-CSF was started one hour after reperfusion at a dose of 15 mg/kg subcutaneously. The motor behavior was measured using Garcia's index and animals were assigned for the assessments of infarction, brain swelling, and mortality rate.

Results: The mortality was 38.46% (control group) and reduced in other groups. Neurological deficit score of control group (40.31 ± 1.56) was significantly lower than in treatment groups. The total cerebral infarct volume of treatment group was significantly lower than control group (43.96 ± 44.05 mm3). Treatment with hypothermy plus G-CSF (2.69 ± 0.24%) could significantly reduce brain swelling volume than other treatment groups.

Conclusion: Our major finding is that mild hypothermic treatment plus G-CSF significantly reduced mortality rate and edema and improved neurological function. The results suggest that the combination of hypothermia and G-CSF is more effectively than other treatment groups being used alone.

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Related in: MedlinePlus

Representative of brain slices stained with triphenyltetrazolium chloride in different groups. Ischemic regions are colored white (light) and non-ischemic region are red (dark). G-CSF, granulocyte colony-stimulating factor
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Figure 1: Representative of brain slices stained with triphenyltetrazolium chloride in different groups. Ischemic regions are colored white (light) and non-ischemic region are red (dark). G-CSF, granulocyte colony-stimulating factor

Mentions: Assessment of cerebral infarction and brain swelling. For defining the size of cerebral infarction, the animals were euthanized under ketamine (44 mg/kg, i.p.) and xylazine (13 mg/kg, i.p.) anesthesia. The brain was then rapidly removed, cut into 2-mm thick coronal sections by using brain matrix, stained with 2,3,5-triphenyltetrazolium chloride at room temperature for 30 minutes and then fixed in 10% buffered formalin [17, 18]. The infarct area on each slice was determined by using a Canon camera (IXUS 1000 HS, 10×), and the infarct areas (mm2) were calculated to obtain the infarct volumes per brain (mm3) by Image J 1.46r software (NIH, Wayne Rasband, USA) (Fig. 1). Infarct volumes were expressed as a percentage of the contralateral hemisphere volume by using an “indirect method” (area of intact contralateral [right] hemisphere minus area of intact regions of the ipsilateral [left] hemisphere) to compensate for edema formation in the ipsilateral hemisphere [17, 19]. Percentage of brain swelling was derived from volumetric growth of the ischemic hemisphere in comparison to the intact one as percentage of brain swelling (edema) = [(right hemisphere’s volume/left hemisphere’s volume)-1] ×100 [20].


Effect of combination therapy using hypothermia and granulocyte colony-stimulating factor in a rat transient middle cerebral artery occlusion model.

Ghahari L, Safari M, Joghataei MT, Mehdizadeh M, Soleimani M - Iran. Biomed. J. (2014)

Representative of brain slices stained with triphenyltetrazolium chloride in different groups. Ischemic regions are colored white (light) and non-ischemic region are red (dark). G-CSF, granulocyte colony-stimulating factor
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4225064&req=5

Figure 1: Representative of brain slices stained with triphenyltetrazolium chloride in different groups. Ischemic regions are colored white (light) and non-ischemic region are red (dark). G-CSF, granulocyte colony-stimulating factor
Mentions: Assessment of cerebral infarction and brain swelling. For defining the size of cerebral infarction, the animals were euthanized under ketamine (44 mg/kg, i.p.) and xylazine (13 mg/kg, i.p.) anesthesia. The brain was then rapidly removed, cut into 2-mm thick coronal sections by using brain matrix, stained with 2,3,5-triphenyltetrazolium chloride at room temperature for 30 minutes and then fixed in 10% buffered formalin [17, 18]. The infarct area on each slice was determined by using a Canon camera (IXUS 1000 HS, 10×), and the infarct areas (mm2) were calculated to obtain the infarct volumes per brain (mm3) by Image J 1.46r software (NIH, Wayne Rasband, USA) (Fig. 1). Infarct volumes were expressed as a percentage of the contralateral hemisphere volume by using an “indirect method” (area of intact contralateral [right] hemisphere minus area of intact regions of the ipsilateral [left] hemisphere) to compensate for edema formation in the ipsilateral hemisphere [17, 19]. Percentage of brain swelling was derived from volumetric growth of the ischemic hemisphere in comparison to the intact one as percentage of brain swelling (edema) = [(right hemisphere’s volume/left hemisphere’s volume)-1] ×100 [20].

Bottom Line: Treatment with hypothermy plus G-CSF (2.69 ± 0.24%) could significantly reduce brain swelling volume than other treatment groups.Our major finding is that mild hypothermic treatment plus G-CSF significantly reduced mortality rate and edema and improved neurological function.The results suggest that the combination of hypothermia and G-CSF is more effectively than other treatment groups being used alone.

View Article: PubMed Central - PubMed

Affiliation: Dept. of Anatomy, Medical School, Iran University of Medical Science, Tehran, Iran. mansourehsoleimani@gmail.com.

ABSTRACT

Background: Stroke is the third leading cause of death. Hypothermia has been recognized as an effective method in reducing brain injury. In this study, we assessed the effects of granulocyte colony-stimulating factor (G-CSF) as a neuroprotective agent and mild hypothermia on mortality, behavioral function, infarct volume, and brain edema in Wistar rats.

Methods: Forty male rats were used in five groups (eight rats in each group): control, hypothermy, G-CSF, combination hypothermy + CSF, and sham. Rats were anesthetized by injection of chloral hydrate (400 mg/kg) intraperitoneally. Transient cerebral ischemia was induced by 60-min intraluminal occlusion of left middle cerebral artery. Hypothermia, initiated at the time of reperfusion and G-CSF was started one hour after reperfusion at a dose of 15 mg/kg subcutaneously. The motor behavior was measured using Garcia's index and animals were assigned for the assessments of infarction, brain swelling, and mortality rate.

Results: The mortality was 38.46% (control group) and reduced in other groups. Neurological deficit score of control group (40.31 ± 1.56) was significantly lower than in treatment groups. The total cerebral infarct volume of treatment group was significantly lower than control group (43.96 ± 44.05 mm3). Treatment with hypothermy plus G-CSF (2.69 ± 0.24%) could significantly reduce brain swelling volume than other treatment groups.

Conclusion: Our major finding is that mild hypothermic treatment plus G-CSF significantly reduced mortality rate and edema and improved neurological function. The results suggest that the combination of hypothermia and G-CSF is more effectively than other treatment groups being used alone.

Show MeSH
Related in: MedlinePlus