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The collagenase model of intracerebral hemorrhage in awake, freely moving animals: The effects of isoflurane

Wilkinson, Cassandra M. ; Kalisvaart, Anna C.J. ; Kung, Tiffany F.C. ; Maisey, D. Ryan ; Klahr, Ana C. ; Dickson, Clayton T. ; Colbourne, Frederick

Brain research, 2020-02, Vol.1728, p.146593, Article 146593 [Peer Reviewed Journal]

Netherlands: Elsevier B.V

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  • Title:
    The collagenase model of intracerebral hemorrhage in awake, freely moving animals: The effects of isoflurane
  • Author: Wilkinson, Cassandra M. ; Kalisvaart, Anna C.J. ; Kung, Tiffany F.C. ; Maisey, D. Ryan ; Klahr, Ana C. ; Dickson, Clayton T. ; Colbourne, Frederick
  • Subjects: Anesthetic ; Animals ; Blood Glucose - metabolism ; Cerebral Hemorrhage - chemically induced ; Cerebral Hemorrhage - physiopathology ; Cerebral Hemorrhage - surgery ; Collagenases - administration & dosage ; Collagenases - pharmacology ; Disease Models, Animal ; Electroencephalography ; Hematoma ; Intracerebral hemorrhage ; Isoflurane ; Isoflurane - pharmacology ; Male ; Pain ; Rats ; Rats, Sprague-Dawley ; Seizures - chemically induced ; Weight Loss
  • Is Part Of: Brain research, 2020-02, Vol.1728, p.146593, Article 146593
  • Description: •We present a method for inducing ICH in awake animals.•We used telemetry to examine the effect of isoflurane on physiology after ICH.•Physiological confounds induced by isoflurane resolve within minutes to hours.•Post-ICH pain levels were comparable in anesthetized and non-anesthetized models. Intracerebral hemorrhage (ICH) is a devastating stroke often modelled in rats. Isoflurane anesthetic, commonly used in preclinical research, affects general physiology (e.g., blood pressure) and electrophysiology (e.g., burst suppression) in many ways. These physiological changes may detract from the clinical relevance of the model. Here, we revised the standard collagenase model to produce an ICH in rats without anesthetic. Guide cannulas were implanted stereotaxically under anesthetic. After 3 days of recovery, collagenase was infused through an internal cannula into the striatum of animals randomly assigned to the non-anesthetized or isoflurane group. We assessed whether isoflurane affected hematoma volume, core temperature, movement activity, pain, blood pressure, and seizure activity. With a small ICH, there was a hematoma volume increased from 8.6 (±3.3, 95% confidence interval) µL in anesthetized rats to 13.2 (±3.1) µL in non-anesthetized rats (P = 0.008), but with a larger ICH, hematoma volumes were similar. Isoflurane decreased temperature by 1.3 °C (±0.16 °C, P < 0.001) for 2 h and caused a 35.1 (±1.7) mmHg group difference in blood pressure (P < 0.007) for 12 m. Blood glucose increased twofold after isoflurane procedures (P < 0.001). Pain, as assessed with the rat grimace scale, did not differ between groups. Seizure incidence rate (62.5%) in non-anesthetized ICH rats was similar to historic amounts (61.3%). In conclusion, isoflurane appears to have some significant and injury size-dependent effects on the collagenase model. Thus, when anesthetic effects are a known concern, the use of the standardized cannula infusion approach is scientifically and ethically acceptable.
  • Publisher: Netherlands: Elsevier B.V
  • Language: English

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