Selective therapeutic cooling: To maximize benefits and minimize side effects related to hypothermia

2021 ◽  
pp. 0271678X2110559
Author(s):  
Di Wu ◽  
Jian Chen ◽  
Xuxiang Zhang ◽  
Roxanne Ilagan ◽  
Yuchuan Ding ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Side Effects ◽  
Therapeutic Hypothermia ◽  
Closed Loop ◽  
Infarct Volume ◽  
Stroke Model ◽  
Promising Technique ◽  
Major Step ◽  
Catheter System ◽  
Brain Reperfusion

Selective therapeutic cooling is a promising technique for reducing final infarct volume and improving outcomes in ischemic stroke, especially as research regarding brain reperfusion continues to be explored. A recent study provided promising results on the safety and feasibility of selective therapeutic hypothermia via a closed-loop cooling catheter system for intra-carotid blood cooling in an ovine stroke model, but they failed to find efficacy of this method in this model. It is a major step forward from bench to bed side, but enhancing benefits of selective therapeutic cooling may need to take into account a more targeted induction of brain hypothermia and should mitigate potential side effects related to inducing hypothermia.

scholarly journals Stroke neuroprotection revisited: Intra-arterial verapamil is profoundly neuroprotective in experimental acute ischemic stroke

2015 ◽  
Vol 36 (4) ◽  
pp. 721-730 ◽  
Author(s):  
Michael E Maniskas ◽  
Jill M Roberts ◽  
Ishi Aron ◽  
Justin F Fraser ◽  
Gregory J Bix
Keyword(s):  
Ischemic Stroke ◽  
Side Effects ◽  
Channel Blocker ◽  
Infarct Volume ◽  
Stroke Model ◽  
Neuroprotective Effects ◽  
Injection Volume ◽  
Cellular Apoptosis ◽  
Systemic Side Effects

While clinical trials have now solidified the role of thrombectomy in emergent large vessel occlusive stroke, additional therapies are needed to optimize patient outcome. Using our previously described experimental ischemic stroke model for evaluating adjunctive intra-arterial drug therapy after vessel recanalization, we studied the potential neuroprotective effects of verapamil. A calcium channel blocker, verapamil is often infused intra-arterially by neurointerventionalists to treat cerebral vasospasm. Such a direct route of administration allows for both focused targeting of stroke-impacted brain tissue and minimizes potential systemic side effects. Intra-arterial administration of verapamil at a flow rate of 2.5 µl/min and injection volume of 10 µl immediately after middle cerebral artery recanalization in C57/Bl6 mice was shown to be profoundly neuroprotective as compared to intra-arterial vehicle-treated stroke controls. Specifically, we noted a significant (P ≤ 0.05) decrease in infarct volume, astrogliosis, and cellular apoptosis as well as a significant increase in neuronal survival and functional outcome over seven days. Furthermore, intra-arterial administration of verapamil was well tolerated with no hemorrhage, systemic side effects, or increased mortality. Thus, verapamil administered intra-arterially immediately following recanalization in experimental ischemic stroke is both safe and neuroprotective and merits further study as a potential therapeutic adjunct to thrombectomy.

scholarly journals Intranasal salvinorin A improves neurological outcome in rhesus monkey ischemic stroke model using autologous blood clot

2020 ◽  
pp. 0271678X2093813
Author(s):  
Longfei Wu ◽  
Di Wu ◽  
Jian Chen ◽  
Chunhua Chen ◽  
Tianqi Yao ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Rhesus Monkeys ◽  
Infarct Volume ◽  
Blood Clot ◽  
Autologous Blood ◽  
Control Group ◽  
Stroke Model ◽  
Neurological Outcomes ◽  
Observation Period ◽  
Autologous Blood Clot

Salvinorin A (SA) exerts neuroprotection and improves neurological outcomes in ischemic stroke models in rodents. In this study, we investigated whether intranasal SA administration could improve neurological outcomes in a monkey ischemic stroke model. The stroke model was induced in adult male rhesus monkeys by occluding the middle cerebral artery M2 segment with an autologous blood clot. Eight adult rhesus monkeys were randomly administered SA or 10% dimethyl sulfoxide as control 20 min after ischemia. Magnetic resonance imaging was used to confirm the ischemia and extent of injury. Neurological function was evaluated using the Non-Human Primate Stroke Scale (NHPSS) over a 28-day observation period. SA significantly reduced infarct volume (3.9 ± 0.7 cm3 vs. 7.2 ± 1.0 cm3; P =  0.002), occupying effect (0.3 ± 0.2% vs. 1.4 ± 0.3%; P =  0.002), and diffusion limitation in the lesion (−28.2 ± 11.0% vs. −51.5 ± 7.1%; P =  0.012) when compared to the control group. SA significantly reduced the NHPSS scores to almost normal in a 28-day observation period as compared to the control group ( P =  0.005). Intranasal SA reduces infarct volume and improves neurological outcomes in a rhesus monkey ischemic stroke model using autologous blood clot.

scholarly journals Dodecafluoropentane Emulsion Decreases Infarct Volume in a Rabbit Ischemic Stroke Model

2012 ◽  
Vol 23 (1) ◽  
pp. 116-121 ◽  
Author(s):  
William C. Culp ◽  
Sean D. Woods ◽  
Robert D. Skinner ◽  
Aliza T. Brown ◽  
John D. Lowery ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Infarct Volume ◽  
Stroke Model

Abstract No. 53: Dodecafluoropentane emulsion decreases infarct volume in a rabbit ischemic stroke model

2011 ◽  
Vol 22 (3) ◽  
pp. S26
Author(s):  
W.C. Culp ◽  
P.K. Roberson ◽  
S.D. Woods ◽  
R. Flores ◽  
J.D. Lowery ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Infarct Volume ◽  
Stroke Model

Abstract T MP16: Impact of Circadian Clock Disruption on Infarct Volume in an Ischemic Stroke Model

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
David Earnest ◽  
Jason Coffman ◽  
Nichole Neuendorff ◽  
Amutha Selvamani ◽  
Farida Sohrabji
Keyword(s):  
Ischemic Stroke ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
The Body ◽  
Female Rats ◽  
Stroke Model ◽  
Young Females ◽  
Functional Deficits ◽  
Before And After ◽  
Estrous Cyclicity

Background: At perimenopause, women show increasing incidence of ischemic stroke and poor prognosis for recovery, suggesting that declining ovarian steroid levels alter the risk for neurovascular disease. Peripheral circadian clocks throughout the body may provide integral links between cycling levels of estrogen and neuroprotective responses. Circadian rhythm disruption may be a key factor coupling risk factors (ie, diabetes, obesity) to cardiovascular pathologies. Thus, the present study used an ischemic stroke model to determine whether environmental disruption of circadian rhythms in young adult female rats modulates estrous cyclicity and induces corresponding increases stroke volume and functional deficits similar to that observed in middle-aged females. Methods: Adult (5 mo) female rats were exposed for 8wks to either a fixed or shifted (12hr advance/5d) LD 12:12 cycle and then subjected to middle cerebral artery occlusion (MCAo). Pre and post sensorimotor testing was performed to assess functional deficits. Animals were terminated at 5d post MCAo. Brains processed for histological analysis of infarct volume. Before and after experimental manipulations, estrous cyclicity was assessed via vaginal smears in parallel groups of animals. Results: Circadian activity rhythms stably entrained to the fixed LD cycle but were severely disrupted in shifted LD rats. In contrast to the regular estrous cycles (~7d) in fixed LD animals, cyclicity was abolished and persistent estrous was evident in all shifted LD rats. Total infarct volume in shifted LD rats (0.47) was significantly increased (p<0.05) relative to that observed in fixed LD controls (0.27). Sensorimotor testing revealed a similar trend in which MCAo-induced functional deficits in shifted LD animals were greater than those in fixed LD rats. Conclusion: These results suggest that the loss of estrous cyclicity in young females due to circadian disruption exacerbates stroke outcomes, supporting the hypothesis that in females, middle-age may precipitate circadian disturbances that link reproductive aging to pathological changes in neuroprotective responses to injury. Supported by AHA 14GRNT18370013 to DE

scholarly journals Selective intra-carotid blood cooling in acute ischemic stroke: A safety and feasibility study in an ovine stroke model

2021 ◽  
pp. 0271678X2110249
Author(s):  
Giorgio FM Cattaneo ◽  
Andrea M Herrmann ◽  
Sebastian A Eiden ◽  
Manuela Wieser ◽  
Elias Kellner ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Carotid Artery ◽  
Acute Ischemic Stroke ◽  
Neurological Outcome ◽  
Artery Occlusion ◽  
Control Group ◽  
Stroke Model ◽  
Primary Endpoints ◽  
Neuroprotective Strategy ◽  
Vessel Patency

Selective therapeutic hypothermia (TH) showed promising preclinical results as a neuroprotective strategy in acute ischemic stroke. We aimed to assess safety and feasibility of an intracarotid cooling catheter conceived for fast and selective brain cooling during endovascular thrombectomy in an ovine stroke model. Transient middle cerebral artery occlusion (MCAO, 3 h) was performed in 20 sheep. In the hypothermia group (n = 10), selective TH was initiated 20 minutes before recanalization, and was maintained for another 3 h. In the normothermia control group (n = 10), a standard 8 French catheter was used instead. Primary endpoints were intranasal cooling performance (feasibility) plus vessel patency assessed by digital subtraction angiography and carotid artery wall integrity (histopathology, both safety). Secondary endpoints were neurological outcome and infarct volumes. Computed tomography perfusion demonstrated MCA territory hypoperfusion during MCAO in both groups. Intranasal temperature decreased by 1.1 °C/3.1 °C after 10/60 minutes in the TH group and 0.3 °C/0.4 °C in the normothermia group (p < 0.001). Carotid artery and branching vessel patency as well as carotid wall integrity was indifferent between groups. Infarct volumes (p = 0.74) and neurological outcome (p = 0.82) were similar in both groups. Selective TH was feasible and safe. However, a larger number of subjects might be required to demonstrate efficacy.

scholarly journals Development of a photochemical thrombosis investigation system to obtain a rabbit ischemic stroke model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoonhee Kim ◽  
Yoon Bum Lee ◽  
Seung Kuk Bae ◽  
Sung Suk Oh ◽  
Jong-ryul Choi
Keyword(s):  
Ischemic Stroke ◽  
Brain Damage ◽  
Rabbit Model ◽  
Specific Area ◽  
Brain Atlas ◽  
Rabbit Brain ◽  
Stroke Model ◽  
Triphenyltetrazolium Chloride ◽  
Induction System

AbstractPhotochemical thrombosis is a method for the induction of ischemic stroke in the cerebral cortex. It can generate localized ischemic infarcts in the desired region; therefore, it has been actively employed in establishing an ischemic stroke animal model and in vivo assays of diagnostic and therapeutic techniques for stroke. To establish a rabbit ischemic stroke model and overcome the shortcoming of previous studies that were difficult to build a standardized photothrombotic rabbit model, we developed a photochemical thrombosis induction system that can produce consistent brain damage on a specific area. To verify the generation of photothrombotic brain damage using the system, longitudinal magnetic resonance imaging, 2,3,5-triphenyltetrazolium chloride staining, and histological staining were applied. These analytical methods have a high correlation for ischemic infarction and are appropriate for analyzing photothrombotic brain damage in the rabbit brain. The results indicated that the photothrombosis induction system has a main advantage of being accurately controlled a targeted region of photothrombosis and can produce cerebral hemisphere lesions on the target region of the rabbit brain. In conjugation with brain atlas, it can induce photochemical ischemic stroke locally in the part of the brain that is responsible for a particular brain function and the system can be used to develop animal models with degraded specific functions. Also, the photochemical thrombosis induction system and a standardized rabbit ischemic stroke model that uses this system have the potential to be used for verifications of biomedical techniques for ischemic stroke at a preclinical stage in parallel with further performance improvements.

Sign in / Sign up

Export Citation Format

Share Document