The effect of heliox treatment in a rat model of focal transient cerebral ischemia

Pan, Y. Albert; Zhang, Haibo; Acharya, Aninda B.; Cruz‐Flores, Salvador; Panneton, W. Michael

doi:10.1016/j.neulet.2011.04.048

Cited by 29 publications

(27 citation statements)

References 27 publications

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“…20 In adult rat stroke models, delayed treatment up to 3 hours is neuroprotective. [21][22][23] Our aim was to investigate in moderate and severe unilateral brain injury in neonatal rats the effect of HT, the optimal duration of HT, and the effective time window of HT.Background and Purpose-Hypothermia (HT) for neonatal hypoxic-ischemic encephalopathy is advised to start within the first 6 hours after birth. There is some clinical evidence that HT is more effective against moderate than against severe hypoxic-ischemic encephalopathy, but it is unknown whether delayed HT beyond 6 hours is effective or even injurious.…”

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confidence: 99%

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Immediate Hypothermia Is Not Neuroprotective After Severe Hypoxia-Ischemia and Is Deleterious When Delayed by 12 Hours in Neonatal Rats

Sabir

Scull-Brown²,

Liu³

et al. 2012

Stroke

137

152

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T herapeutic hypothermia (HT) has become standard treatment for term newborns experiencing perinatal asphyxia.1 Randomized controlled trials have shown that HT significantly improves outcome after hypoxia-ischemia (HI). [2][3][4][5][6] Meta-analysis of these suggests that HT improves outcome more in the group with moderate rather than severe HI encephalopathy.7 HI encephalopathy develops during different phases. 8 Initial reperfusion restores cellular energy metabolism in ≈30 to 60 minutes. A latent phase of 6 to 12 hours follows, in which cellular energy metabolism is fully or partially restored 9 before a secondary decline in energy failure may occur. This secondary phase is characterized by excessive entry of Ca 2+ into cells, free radical production, excitotoxic amino acid release, inflammation, and activation of apoptotic pathways, [10][11][12] commencing within 24 hours and lasting days or weeks. These phases of injury and recovery are not strictly sequential, might overlap, and are likely to be changed by severity of injury or other conditions. 13 As previously shown in different animal models, HT during reperfusion and the latent phase is neuroprotective. [14][15][16] Clinical guidelines recommend that HT should be started within the first 6 hours after birth based on findings in a term-equivalent fetal sheep HI model 16,17 showing significant neuroprotection when HT was initiated before 5.5 hours after cerebral injury.8 There are few studies published about the effect of HT initiated late after HI of different severity, 8,18,19 and no study asks whether HT might increase injury if started very late. There might be species, age, and injury differences. In newborn pigs, delaying HT by 3 hours was ineffective. 20 In adult rat stroke models, delayed treatment up to 3 hours is neuroprotective. [21][22][23] Our aim was to investigate in moderate and severe unilateral brain injury in neonatal rats the effect of HT, the optimal duration of HT, and the effective time window of HT.Background and Purpose-Hypothermia (HT) for neonatal hypoxic-ischemic encephalopathy is advised to start within the first 6 hours after birth. There is some clinical evidence that HT is more effective against moderate than against severe hypoxic-ischemic encephalopathy, but it is unknown whether delayed HT beyond 6 hours is effective or even injurious. Methods-One-hundred seven 7-day-old rat pups underwent unilateral hypoxia-ischemia of moderate severity. Pups were randomized to receive 5 hours of normothermia (NT) or HT starting immediately, 3 hours, 6 hours, or 12 hours after the 90-minute hypoxic period. One-hundred five 7-day-old rat pups underwent severe hypoxia-ischemia lasting 150 minutes, followed by the same group design as mentioned. Relative area loss of the left/right hemisphere was measured after 1 week of survival. Results-In the moderate NT group, the mean area loss of the left hemisphere was 40.5%. Materials and Methods ProceduresAll procedures were performed under Home Office license in accordance with United Kingdom r...

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confidence: 99%

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confidence: 99%

Immediate Hypothermia Is Not Neuroprotective After Severe Hypoxia-Ischemia and Is Deleterious When Delayed by 12 Hours in Neonatal Rats

Sabir

Scull-Brown²,

Liu³

et al. 2012

Stroke

137

152

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“…Furthermore, late helium treatment administered 30-60 min after reperfusion? did not elicit protection [113]. Physiological parameters such as blood pressure, heart rate were similar between the experimental and control groups [107].…”

Section: Gaseous Hypothermiamentioning

confidence: 86%

Drug-Induced Hypothermia in Stroke Models: Does it Always Protect?

Zhang¹,

Wang²,

Zhao³

et al. 2013

CNSNDDT

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Ischemic stroke is a common neurological disorder lacking a cure. Recent studies show that therapeutic hypothermia is a promising neuroprotective strategy against ischemic brain injury. Several methods to induce therapeutic hypothermia have been established; however, most of them are not clinically feasible for stroke patients. Therefore, pharmacological cooling is drawing increasing attention as a neuroprotective alternative worthy of further clinical development. We begin this review with a brief introduction to the commonly used methods for inducing hypothermia; we then focus on the hypothermic effects of eight classes of hypothermia-inducing drugs: the cannabinoids, opioid receptor activators, transient receptor potential vanilloid, neurotensins, thyroxine derivatives, dopamine receptor activators, hypothermia-inducing gases, adenosine, and adenine nucleotides. Their neuroprotective effects as well as the complications associated with their use are both considered. This article provides guidance for future clinical trials and animal studies on pharmacological cooling in the setting of acute stroke. KeywordsBrain ischemia; Hypothermic; Neuroprotection; Pharmacological cooling Send correspondence to: Dr. Feng Zhang, Department of Neurology, University of Pittsburgh School of Medicine, 3500 Terrace Street, Pittsburgh, PA, 15213, USA, Telephone: 412-383-7604, Fax: 412-648-1239, zhanfx2@upmc.edu NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 1. Hypothermia and strokes IntroductionTherapeutic hypothermia is defined as a 2-6°C reduction of core body temperature [1][2][3] and is a promising neuroprotective approach against brain injury induced by strokes. In hemorrhagic stroke, hypothermia reduces brain edema [4,5] and improves neurologic function [4][5][6][7]. In ischemic stroke, hypothermia is also protective, which has been proven in randomized clinical trials in human cardiac arrest and in animal studies of focal and global ischemia [8,9]. However, the impact of hypothermia on patients with acute ischemic stroke still needs to be explored [10]. During the past decades, studies on hypothermia and ischemic stroke have suggested that the required amplitude of protective hypothermia depends on its time of initiation relative to stroke onset, duration, and depth of hypothermia [1,9,11]. Optimal protection is typically gained when hypothermia is induced as early as possible after stroke onset, with a mild-to-moderate hypothermia of 32 to 35°C that lasts at least one to two hours [1, 2, 12-14]. Protective mechanism of hypothermia in ischemic strokeAlthough hypothermia is effective in protecting against experimental models of ischemic stroke, the precise protective mechanisms are not yet fully understood. It has been suggested that the protective mechanisms are multifold, including reductions in metabolic rate, cerebral blood flow, blood-brain barrier damage, as well as decreases in excitotoxicity, apoptosis, inflammation and free radical production [15]. On average, hypothermia red...

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“…δ-opioid agonist (79) Reduced inflammation 40 mg/kg -4.13 ± 0.20 °C NMRI mice (33,84,85) DADLE δ-opioid agonist Toxicity at 10 mg/kg: (33) 6 mg/kg -3.2 ± 0.20 °C (33) Mice (84) ↓ Blood pressure (85) Arrhythmia Neurotensin (90) NT69L Neurotensin analog (92) Reduced apoptosis, reduced inflammation 2 mg/kg -2 -5 °C Wistar rats (90) Anti-shivering thermoregulatory effects (86) no cold intolerance response (113,114) Heliox Unknown (113,114) Maintenance of animal temperature at 37 °C still elicited neuroprotection 70%/30% helium/oxygen Sprague-Dawley rats (114) Improved regulation of mitochondrial respiration (114) Reduced adverse effects of nitrogen, inflammation, coagulant actions (116) Hydrogen (119,122) AMP (122) A1 receptor agonist (119) No neuroprotection (119) Larger infarct volume (119) 4 mmol/kg (~1.39 g/kg) (119) 33.1 ± 0.7 °C (119) Sprague-Dawley rats (122) C57/BI6 mice (122) Reduced infarct volume ↑ Incidences of hemorrhagic transformation (122) 50-100 mg/ kg (122) Reduced mortality seizure, and, mortality ↓ Blood pressure ↓ Heart rate Hyperglycemia…”

Section: Snc-80mentioning

confidence: 99%

“…Pan et al 119 and Pan et al 120 have shown that the neuroprotective effect of heliox may be independent from hypothermia seeing as the constant maintenance of animal temperature at 37 °C still elicited neuroprotection. The mechanism of heliox treatment remains largely unclear; aside from helium-induced hypothermia, some of the other mechanisms that were proposed include regulation of mitochondrial respiration, reduction of adverse effects due to nitrogen, and anti-inflammatory and anticoagulant actions occurring after ischemia-reperfusion injury.…”

Section: Dopamine Receptor Activatorsmentioning

confidence: 99%

Pharmacological hypothermia: a potential for future stroke therapy?

Liu

Khan

et al. 2016

Neurological Research

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Mild physical hypothermia after stroke has been associated with positive outcomes. Despite the well-studied beneficial effects of hypothermia in the treatment of stroke, lack of precise temperature control, intolerance for the patient, and immunosuppression are some of the reasons which limit its clinical translation. Pharmacologically induced hypothermia has been explored as a possible treatment option following stroke in animal models. Currently, there are eight classes of pharmacological agents/agonists with hypothermic effects affecting a multitude of systems including cannabinoid, opioid, transient receptor potential vanilloid 1 (TRPV1), neurotensin, thyroxine derivatives, dopamine, gas, and adenosine derivatives. Interestingly, drugs in the TRPV1, neurotensin, and thyroxine families have been shown to have effects in thermoregulatory control in decreasing the compensatory hypothermic response during cooling. This review will briefly present drugs in the eight classes by summarizing their proposed mechanisms of action as well as side effects. Reported thermoregulatory effects of the drugs will also be presented. This review offers the opinion that these agents may be useful in combination therapies with physical hypothermia to achieve faster and more stable temperature control in hypothermia.

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The effect of heliox treatment in a rat model of focal transient cerebral ischemia

Cited by 29 publications

References 27 publications

Immediate Hypothermia Is Not Neuroprotective After Severe Hypoxia-Ischemia and Is Deleterious When Delayed by 12 Hours in Neonatal Rats

Immediate Hypothermia Is Not Neuroprotective After Severe Hypoxia-Ischemia and Is Deleterious When Delayed by 12 Hours in Neonatal Rats

Drug-Induced Hypothermia in Stroke Models: Does it Always Protect?

Pharmacological hypothermia: a potential for future stroke therapy?

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