Keck School Faculty

Patrick Lyden

Patrick Lyden

Visiting Professor of Physiology and Neuroscience and Neurology
ZNI 201, 1501 San Pablo Street Health Sciences Campus Los Angeles


Cedars-Sinai Medical Center: Faculty Teaching Award, 2020

American Heart Association/American Stroke Association: AHA/ASA William M. Feinberg Award for Excellence in Clinical Stroke , 2019

UT Houston: Gladys & George T. Abell Lecturship in Neurology, 2019

UCSD: Department of Neurosciences Award for Outstanding Teaching, 2014

University of Iowa: Adolf L. Sahs, MD Memorial Visiting Lecturer, 2011

American Heart Association, San Diego Affiliate: Heart of Gold Award, 2002

: Best Doctors in America, 2001-now

Acute ophthalmic artery occlusion in a COVID-19 patient on apixaban J Stroke Cerebrovasc Dis. 2020 Aug; 29(8):104982. . View in PubMed

3K3A-Activated Protein C Variant Does Not Interfere With the Plasma Clot Lysis Activity of Tenecteplase Stroke. 2020 Jul; 51(7):2236-2239. . View in PubMed

COVID-19 hypothesis: Activated protein C for therapy of virus-induced pathologic thromboinflammation Res Pract Thromb Haemost. 2020 May; 4(4):506-509. . View in PubMed

Assessing Cerebrovascular Hemodynamics Using Transcranial Doppler in Patients with Mechanical Circulatory Support Devices J Neuroimaging. 2020 May; 30(3):297-302. . View in PubMed

Differential Expression of Vascular Endothelial Growth Factor-A165 Isoforms Between Intracranial Atherosclerosis and Moyamoya Disease J Stroke Cerebrovasc Dis. 2019 Feb; 28(2):360-368. . View in PubMed

Differential effects of hypothermia on neurovascular unit determine protective or toxic results: Toward optimized therapeutic hypothermia J Cereb Blood Flow Metab. 2019 09; 39(9):1693-1709. . View in PubMed

Final Results of the RHAPSODY Trial: A Multi-Center, Phase 2 Trial Using a Continual Reassessment Method to Determine the Safety and Tolerability of 3K3A-APC, A Recombinant Variant of Human Activated Protein C, in Combination with Tissue Plasminogen Activator, Mechanical Thrombectomy or both in Moderate to Severe Acute Ischemic Stroke Ann Neurol. 2019 01; 85(1):125-136. . View in PubMed

Differential expression of circulating exosomal microRNAs in refractory intracranial atherosclerosis associated with antiangiogenesis Sci Rep. 2019 12 19; 9(1):19429. . View in PubMed

Acute neuropathological consequences of short-term mechanical ventilation in wild-type and Alzheimer's disease mice Crit Care. 2019 02 22; 23(1):63. . View in PubMed

Can an anticoagulant reduce brain hemorrhage: Invited comment on "Dabigatran reduces endothelial permeability through inhibition of thrombin-induced cytoskeleton reorganization" Thromb Res. 2018 Jun 12. . View in PubMed

Absolute risk and predictors of the growth of acute spontaneous intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data Lancet Neurol. 2018 10; 17(10):885-894. . View in PubMed

Effects of alteplase for acute stroke according to criteria defining the European Union and United States marketing authorizations: Individual-patient-data meta-analysis of randomized trials Int J Stroke. 2018 02; 13(2):175-189. . View in PubMed

Cerebral Pulsatility Index Is Elevated in Patients with Elevated Right Atrial Pressure J Neuroimaging. 2018 01; 28(1):95-98. . View in PubMed

Cerebral microemboli detection for monitoring structural cardiac disease Neurol Clin Pract. 2017 Oct; 7(5):409-412. . View in PubMed

Brain Transforming Growth Factor-ß Resists Hypertension Via Regulating Microglial Activation Stroke. 2017 09; 48(9):2557-2564. . View in PubMed

Clinical Studies Targeting Stroke and Ischemic Insults Ther Hypothermia Temp Manag. 2017 03; 7(1):12-15. . View in PubMed

Activated protein C promotes neuroprotection: mechanisms and translation to the clinic Thromb Res. 2016 May; 141 Suppl 2:S62-4. . View in PubMed

Current Advances in the Use of Therapeutic Hypothermia Ther Hypothermia Temp Manag. 2016 Mar; 6(1):2-5. . View in PubMed

Effects of Alteplase for Acute Stroke on the Distribution of Functional Outcomes: A Pooled Analysis of 9 Trials Stroke. 2016 09; 47(9):2373-9. . View in PubMed

Arabic cross cultural adaptation and validation of the National Institutes of Health Stroke Scale J Neurol Sci. 2015 Oct 15; 357(1-2):152-6. . View in PubMed

Clinical studies targeting stroke Ther Hypothermia Temp Manag. 2015 Mar; 5(1):4-8. . View in PubMed

Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials Lancet. 2014 Nov 29; 384(9958):1929-35. . View in PubMed

Challenges of decision making regarding futility in a randomized trial: the Interventional Management of Stroke III experience Stroke. 2014 May; 45(5):1408-14. . View in PubMed

Direct thrombin inhibitor argatroban reduces stroke damage in 2 different models Stroke. 2014 Mar; 45(3):896-9. . View in PubMed

Endovascular therapeutic hypothermia for acute ischemic stroke: ICTuS 2/3 protocol Int J Stroke. 2014 Jan; 9(1):117-25. . View in PubMed

Clinical use of computed tomographic perfusion for the diagnosis and prediction of lesion growth in acute ischemic stroke J Stroke Cerebrovasc Dis. 2014 Jan; 23(1):114-22. . View in PubMed

Does the cognitive measure Cog-4 show improvement among patients treated with thrombolysis after acute stroke? Int J Stroke. 2013 Dec; 8(8):652-6.. View in PubMed

Activated protein C analog protects from ischemic stroke and extends the therapeutic window of tissue-type plasminogen activator in aged female mice and hypertensive rats Stroke. 2013 Dec; 44(12):3529-36. . View in PubMed

Acute Stroke Imaging Research Roadmap II Stroke. 2013 Sep; 44(9):2628-39. . View in PubMed

Determinants of Pneumonia Risk During Endovascular Hypothermia Ther Hypothermia Temp Manag. 2013 Mar; 3(1):24-27. . View in PubMed

Concurrent middle cerebral artery occlusion and intra-arterial drug infusion via ipsilateral common carotid artery catheter in the rat J Neurosci Methods. 2013 Feb 15; 213(1):63-9. . View in PubMed

Eagle syndrome revisited: cerebrovascular complicationsAnn Vasc Surg. 2012 Jul; 26(5):729. e1-5. . View in PubMed

Determinants of effective cooling during endovascular hypothermia Neurocrit Care. 2012 Jun; 16(3):413-20. . View in PubMed

Editorial on "A simple, assumption-free, and clinically interpretable approach for analysis of modified Rankin outcomes" Stroke. 2012 Mar; 43(3):621-2. . View in PubMed

Advanced brain imaging studies should not be performed in patients with suspected stroke presenting within 45 hours of symptom onset. Stroke. 2011 Sep; 42(9):2668-9. . View in PubMed

Commentary: The endovascular procedure-specific neurological examination scheme J Endovasc Ther. 2011 Aug; 18(4):538-9. . View in PubMed

Frequent early cardiac complications contribute to worse stroke outcome in atrial fibrillation Cerebrovasc Dis. 2011; 32(5):454-60. . View in PubMed

ACCESS: acute cerebrovascular care in emergency stroke systems Arch Neurol. 2010 Oct; 67(10):1210-8. . View in PubMed

Disability status at 1 month is a reliable proxy for final ischemic stroke outcome Neurology. 2010 Aug 24; 75(8):688-92. . View in PubMed

Analysis of the National Institute of Neurological Disorders and Stroke tissue plasminogen activator studies following European Cooperative Acute Stroke Study III patient selection criteria J Stroke Cerebrovasc Dis. 2010 Jul-Aug; 19(4):290-3. . View in PubMed

An ethical hierarchy for decision making during medical emergencies Ann Neurol. 2010 Apr; 67(4):434-40. . View in PubMed

Evolution of the thrombolytic treatment window for acute ischemic stroke Curr Neurol Neurosci Rep. 2010 Jan; 10(1):29-33. . View in PubMed

Correlations of neuronal and microvascular densities in murine cortex revealed by direct counting and colocalization of nuclei and vessels J Neurosci. 2009 Nov 18; 29(46):14553-70. . View in PubMed

Delayed detection of atrial fibrillation after ischemic stroke J Stroke Cerebrovasc Dis. 2009 Nov-Dec; 18(6):453-7. . View in PubMed

A randomized, double-blind, placebo-controlled trial to evaluate the efficacy, safety, tolerability, and pharmacokinetic/pharmacodynamic effects of a targeted exposure of intravenous repinotan in patients with acute ischemic stroke: modified Randomized Exposure Controlled Trial (mRECT) Stroke. 2009 Nov; 40(11):3518-25. . View in PubMed

Factors associated with intracerebral hemorrhage after thrombolytic therapy for ischemic stroke: pooled analysis of placebo data from the Stroke-Acute Ischemic NXY Treatment (SAINT) I and SAINT II Trials Stroke. 2009 Sep; 40(9):3067-72. . View in PubMed

Development of the Italian version of the National Institutes of Health Stroke Scale: It-NIHSS Stroke. 2009 Jul; 40(7):2557-9. . View in PubMed

Acute vascular disruption and aquaporin 4 loss after stroke Stroke. 2009 Jun; 40(6):2182-90. . View in PubMed

Active dilation of penetrating arterioles restores red blood cell flux to penumbral neocortex after focal stroke J Cereb Blood Flow Metab. 2009 Apr; 29(4):738-51. . View in PubMed

Can comprehensive stroke centers erase the 'weekend effect'? Cerebrovasc Dis. 2009; 27(2):107-13.. View in PubMed

Stroke. 2008 Dec; 39(12):3335-40. . View in PubMed

Efficacy of site-independent telemedicine in the STRokE DOC trial: a randomised, blinded, prospective study Lancet Neurol. 2008 Sep; 7(9):787-95. . View in PubMed

Effect of endovascular hypothermia on acute ischemic edema: morphometric analysis of the ICTuS trial Neurocrit Care. 2008; 8(1):42-7. . View in PubMed

Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists Circulation. 2007 May 22; 115(20):e478-534. . View in PubMed

Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists Stroke. 2007 May; 38(5):1655-711. . View in PubMed

An expedited code stroke protocol is feasible and safe Stroke. 2006 Dec; 37(12):2935-9. . View in PubMed

Additional outcomes and subgroup analyses of NXY-059 for acute ischemic stroke in the SAINT I trial Stroke. 2006 Dec; 37(12):2970-8. . View in PubMed

Alteplase for acute stroke revisited: the first 10 years Lancet Neurol. 2006 Sep; 5(9):722-4. . View in PubMed

A trial of therapeutic hypothermia via endovascular approach in awake patients with acute ischemic stroke: methodology Acad Emerg Med. 2006 Aug; 13(8):820-7. . View in PubMed

Contraindications of VEGF-based therapeutic angiogenesis: effects on macrophage density and histology of normal and ischemic brains Vascul Pharmacol. 2006 May; 44(5):316-25. . View in PubMed

Beyond subgroup analysis: improving the clinical interpretation of treatment effects in stroke research J Neurosci Methods. 2005 Apr 30; 143(2):209-16. . View in PubMed

A pilot dose-escalation safety study of tenecteplase in acute ischemic stroke Stroke. 2005 Mar; 36(3):607-12. . View in PubMed

Asymptomatic hemorrhagic transformation of cerebral infarction does not worsen long-term outcome J Stroke Cerebrovasc Dis. 2005 Mar-Apr; 14(2):50-4. . View in PubMed

Factor analysis of the National Institutes of Health Stroke Scale in patients with large strokes Arch Neurol. 2004 Nov; 61(11):1677-80. . View in PubMed

Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials Lancet. 2004 Mar 06; 363(9411):768-74. . View in PubMed

Early impairment in consciousness predicts mortality after hemispheric ischemic stroke Crit Care Med. 2004 Jan; 32(1):241-5. . View in PubMed

Early major ischemic changes on computed tomography should not preclude use of tissue plasminogen activator Stroke. 2003 Mar; 34(3):821-2. . View in PubMed

Admission glucose level and clinical outcomes in the NINDS rt-PA Stroke Trial Neurology. 2002 Sep 10; 59(5):669-74. . View in PubMed

Clomethiazole Acute Stroke Study in ischemic stroke (CLASS-I): final results Stroke. 2002 Jan; 33(1):122-8. . View in PubMed

Further randomized controlled trials of tPA within 3 hours are required-not! Stroke 2001 Nov; 32(11):2709-10. . View in PubMed

Angiogenesis after stroke is correlated with increased numbers of macrophages: the clean-up hypothesis J Cereb Blood Flow Metab. 2001 Oct; 21(10):1223-31. . View in PubMed

A simple stereologic method for analysis of cerebral cortical microvessels using image analysis Brain Res Brain Res Protoc. 2001 Aug; 8(1):45-57. . View in PubMed

Apolipoprotein E phenotype and the efficacy of intravenous tissue plasminogen activator in acute ischemic stroke Ann Neurol. 2001 Jun; 49(6):736-44. . View in PubMed

A modified National Institutes of Health Stroke Scale for use in stroke clinical trials: preliminary reliability and validity Stroke. 2001 Jun; 32(6):1310-7. . View in PubMed

Comparison of TNK with wild-type tissue plasminogen activator in a rabbit embolic stroke model Stroke. 2001 Mar; 32(3):748-52. . View in PubMed

Clinical deterioration following improvement in the NINDS rt-PA Stroke Trial Stroke. 2001 Mar; 32(3):661-8. . View in PubMed

Finding the most powerful measures of the effectiveness of tissue plasminogen activator in the NINDS tPA stroke trial Stroke. 2000 Oct; 31(10):2335-41. . View in PubMed

Effect of ganaxolone in a rodent model of cerebral hematoma Stroke. 2000 Jan; 31(1):169-75. . View in PubMed

Criteria for selection of older patients for thrombolytic therapy Clin Geriatr Med. 1999 Nov; 15(4):721-39. . View in PubMed

Stroke. 1999 Nov; 30(11):2355-9. . View in PubMed

Agreement and variability in the interpretation of early CT changes in stroke patients qualifying for intravenous rtPA therapy Stroke. 1999 Aug; 30(8):1528-33. . View in PubMed

Acute medical therapy J Stroke Cerebrovasc Dis. 1999 May-Jun; 8(3):139-45. . View in PubMed

Assessment scales for the evaluation of stroke patients J Stroke Cerebrovasc Dis. 1998 Mar-Apr; 7(2):113-27. . View in PubMed

Effects of hyperbaric oxygen on neurologic outcome for cerebral ischemia in rats Acad Emerg Med. 1998 Jan; 5(1):18-24. . View in PubMed

GABA and neuroprotection Int Rev Neurobiol. 1997; 40:233-58. . View in PubMed

Combination chemotherapy extends the therapeutic window to 60 minutes after stroke J Neurotrauma. 1995 Apr; 12(2):223-30. . View in PubMed

Gait parameters following stroke: a practical assessment J Rehabil Res Dev. 1995 Feb; 32(1):25-31. . View in PubMed

A rapid, reliable, and valid method for measuring infarct and brain compartment volumes from computed tomographic scans Stroke. 1994 Dec; 25(12):2421-8. . View in PubMed

Combination therapy protects ischemic brain in ratsA glutamate antagonist plus a gamma-aminobutyric acid agonist. Stroke. 1994 Jan; 25(1):189-96. . View in PubMed

A critical appraisal of stroke evaluation and rating scales Stroke. 1991 Nov; 22(11):1345-52. . View in PubMed

Cerebral hemorrhagic risk of aspirin or heparin therapy with thrombolytic treatment in rabbits Stroke. 1991 Jul; 22(7):872-6. . View in PubMed

Duplex carotid sonographyPeak systolic velocity in quantifying internal carotid artery stenosis. J Ultrasound Med. 1990 Jun; 9(6):345-9. . View in PubMed

Carotid endarterectomy in a teaching hospital Stroke. 1989 Jul; 20(7):968-9. . View in PubMed

Acute anticoagulation following cardioembolic stroke Stroke. 1989 Jun; 20(6):730-4. . View in PubMed

Delayed emergence of striatal dopaminergic hyperactivity after anterolateral ischemic cortical lesions in humans; evidence from turning behavior Biol Psychiatry. 1989 Feb 01; 25(3):265-74. . View in PubMed

Effects of calcium channel blockers on neurologic outcome after focal ischemia in rabbits Stroke. 1988 Aug; 19(8):1020-6. . View in PubMed

'Crescendo' transient ischemic attacks: clinical and angiographic correlations Neurology. 1988 Feb; 38(2):198-201. . View in PubMed

Glutamate antagonist therapy reduces neurologic deficits produced by focal central nervous system ischemia Arch Neurol. 1988 Feb; 45(2):148-53. . View in PubMed

A model for quantitative evaluation of embolic stroke therapy Brain Res. 1987 Dec 01; 435(1-2):305-9. . View in PubMed

Brain magnetic resonance imaging in the evaluation of lacunar stroke Stroke. 1987 Jul-Aug; 18(4):781-6. . View in PubMed

I am a neurologist with specialty board certification in Vascular Neurology. I have run large, multi-center clinical trials for industry and NIH. I have a laboratory effort that has been funded for over 30 years by NIH, VA and AHA focused on translational pre-clinical stroke modeling, pharmacology, and vascular biology. Our lab has recently focused on the role of thrombin mediating cytotoxicity and cytoprotection in the brain. Also, we have a long-standing interest in pre-clinical models of therapeutic hypothermia, motivated by my role as PI of the largest clinical trial of therapeutic hypothermia for stroke, the ICTuS program. We have considerable experience with a variety of experimental models; behavioral testing; histology; and cell biology. My team and I were recently selected by NINDS to develop the Stroke Preclinical Assessment Network (SPAN) as the Coordinating Center. The SPAN will test 6 novel stroke treatments in a state-of-the-art, rigorous network of expert pre-clinical stroke testing centers. We have considerable experience with a variety of experimental stroke models; behavioral testing; histology; and cell biology. Details follow:

I joined the Justin Zivin lab as a post-doctoral Fellow at the time he published his seminal demonstration that rt-PA powerfully protected neurological function after cerebral embolism (Zivin et al, 1985; Science 230:1289). During a 5-year R29 (NS267883) under Zivin, I created a model of post-embolic hemorrhage and contributed to the development of rt-PA as a clinical therapeutic. I was honored to be selected as the San Diego site PI of the NINDS for rt-PA Acute Stroke Trial (N01-N292332 and N01-NS02377), during which I helped draft the protocol and main results for that landmark trial. I wrote, produced and directed the NIH Stroke Scale training and certification video that has now been viewed by over 2M individuals around the world—I oversaw the clinimetric validation of these video tools. The rt-PA for stroke trial, published in the New England Journal of Medicine in 1995, is one of the most influential trials in the history of modern neurology.

My earliest research focused on agonists of the GABA-A receptor as neuroprotectants, which I demonstrated were at least as powerful in vivo as glutamate channel antagonists. The combination of both classes of drug exhibited powerful synergism. These studies led to several clinical trials for which I was the San Diego site PI. Then, I was chosen to serve as the global principal investigator of the GABA-A agonist clomethiazole trial known as CLASS, the global PI of the CHANT trial, and the North American coordinating investigator for SAINT 1 and SAINT 2.

In later studies, my lab studied angiogeneis, and the potential for angiogenic growth factors to serve as neuroprotectants. We noted a blood-brain barrier effect of VEGF, used in these studies, which led to several studies of angiogenesis (R01 NS43300) as we explored the role of putative neuroprotective growth factors. We eventually discovered that ischemic brain produces angiogenic growth factors to open capillaries and to promote entry of phagocytic macrophages, a phenomenon we labeled “the Clean-up hypothesis”. We showed convincingly that the angiogenesis documented around infarcts serves ONLY the clean-up of necrosis and is not a protective or neo-restorative effect.

During the vascular leakage studies in the lab, we became aware of work showing that thrombin powerfully opens the BBB by a direct effect on endothelial cells and kills neurons and astrocytes. Given our interest in leakage, we began working with thrombin. We also were aware of the seemingly contradictory effect of very-low-dose thrombin to protect brain (pre-conditioning). One of my PhD students noted that neurons expressed prothrombin message, an effect we dismissed at first as lab error. After confirming his results and finding traces of a similar finding in the literature, we began to ask what the purpose could be of neuronal-expressed thrombin. We showed (R01 NS075930) that thrombin powerfully kills cells in a dose-dependent manner via the PAR-1 receptor. Thrombin activity is associated with direct neuron killing during stroke. Thrombin antagonists, such as argatroban, are powerful neuroprotectants, and a clinical trial studied PAR-1 agent 3K3A-APC for which I served as the national PI (U01 NS088312). Argatroban itself is under study as stroke therapy, and I served as the Los Angeles site PI (P50 NS044227, Grotta).

Although these translational results were gratifying, we were left with the question, why does brain make the serum clotting factor prothrombin? We have used oxygen-glucose deprivation (OGD) in cell culture to model cellular responses to stroke or cardiac arrest. In a series of elegant in vitro experiments, my colleague Padmesh Rajput and I have demonstrated the OGD stressed neurons secrete thrombin into the culture media; OGD neuronal conditioned-media causes astrocyte activation; such astrocyte activation can be reproduced with low doses of thrombin; and is blocked by thrombin inhibitors or by knocking down or knocking out PAR-1 from the astrocytes. We then created an inducible, neuron-targeted prothrombin knock out experimental. After inducing the neuronal prothrombin knock out, the region of induced infarction in these experimentals is significantly enlarged and there is greatly reduced evidence of astrocyte activation in the ischemic bed. Taken together, these results suggest the novel hypothesis that neurons produce prothrombin as a distress signal to adjacent astrocytes, which respond with the newly described astrocyte protective response. We are actively engaged in multiple studies to support/refute this hypothesis; extend it to other elements in the NVU; and identify the active agent(s) comprising the astrocyte protective response.

Another area of interest in our laboratory is brain cooling, or therapeutic hypothermia, the most powerful neuroprotectant ever documented in stroke models. Therapeutic hypothermia is of proven benefit for victims of cardiac arrest or neonatal hypoxic-ischemic injury. For over a decade I worked on the ICTuS program (P50 NS044148) to deliver therapeutic hypothermia to patients. In the first trial, ICTuS, we showed that therapeutic hypothermia could be safely delivered with an endovascular cooling catheter. In the ICTuS-L program, we safely combined endovascular cooling with rt-PA. In the ICTuS 2/3 trial we attempted to document efficacy of therapeutic hypothermia and thrombolysis. The trial was stopped early, however, after several other trials of intra-arterial neurothrombectomy were overwhelmingly positive. We revised the ICTuS 3 protocol to accommodate neurothrombectomy, but during analysis of the small ICTuS 2 dataset we noted a troubling trend (not statistically significant) toward pneumonia risk during cooling. Also, other trials were published showing lack of efficacy for therapeutic hypothermia in head trauma, and no discernible difference between 33ºC vs 36ºC target temperatures for hypothermia after cardiac arrest. We asked if we were using therapeutic hypothermia correctly in treating these illnesses. Based on our observations of astrocyte protection of neurons, we asked whether cooling could disrupt the astrocyte mediated protection of neurons. In fact, we showed that hypothermia interferes with the astrocytes, in a graded, temperature-dependent manner. We recently showed that ultra-fast cooling to 33ºC for a short time was more powerful in the MCAo model than longer cooling periods. These exciting and novel data, if confirmed, suggest a reason for the failures of therapeutic hypothermia in some clinical trials. Moreover, our data suggests testable hypotheses about the effects of temperature in modulating NVU protection during ischemia.
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