William Mack, MD

Dr. Mack’s major areas of clinical interest are stroke, brain aneurysms, subarachnoid hemorrhage, arteriovenous malformations (AVMs), arteriovenous fistulas, cavernous malformations, carotid artery disease, intracranial stenosis, and brain tumors. Dr. Mack performs both open surgery and minimally invasive, endovascular procedures for cerebrovascular disorders.

Dr. Mack is a faculty member of the Neuroscience Graduate Program and is the Principal Investigator and Director of the Cerebrovascular Laboratory in the Zilkha Neurogenetic Institute. He receives NIH R01 funding for his laboratory research. Dr. Mack’s scientific interests are focused on translational efforts to treat ischemic and hemorrhagic stroke. Laboratory investigations concentrate on the pathophysiology of cerebral ischemia and inflammatory modulation. Using the information and experience gained in the laboratory, Dr. Mack is working to develop new technologies, techniques, and therapies to directly improve the clinical care administered to stroke patients.

William Mack, MD, received his Bachelor degree with honors from Cornell University. He then attended Columbia University, College of Physicians and Surgeons, where he graduated from medical school (Alpha Omega Alpha) and completed Neurosurgical residency training. During residency, he spent one year performing a post-doctoral cerebrovascular research fellowship under Drs. David J. Pinsky and E. Sander Connolly Jr. at Columbia University. Following residency, Dr. Mack completed an Interventional Neuroradiology/ Neuroendovascular Surgery fellowship at UCLA.

Dr. Mack is board certified by the American Board of Neurological Surgery (FAANS) and is a fellow of the American Heart Association (FAHA) and. He is a committee member on the executive council of the Congress of Neurological Surgeons/ American Association of Neurological Surgeons’ Cerebrovascular Section. Dr. Mack serves as an Associate Editor of the Journal of Neurointerventional Surgery and on the editorial board of World Neurosurgery.

• Synergistic white matter injury from diesel exhaust particulate and chronic cerebral hypoperfusion exposures: Interaction between the Nogo/NgR1 receptor pathway and extravascular fibrinogen toxicity
  NIH · RF1NS130681 · Sep 20, 2022 – Aug 31, 2027 · Role: Principal Investigator
• Activated protein C mechanisms of brain white matter protection and new therapies for brain white matter ischemic injury
  NIH · R01NS117827 · Jul 15, 2020 – Apr 30, 2026 · Role: Principal Investigator
• Translational potential of the internalization of Nogo-A receptor to enhance axonal regeneration after stroke
  NIH · R21NS116720 · Jul 1, 2020 – Jun 30, 2022 · Role: Co-Principal Investigator
• USC Neurosurgery Research and Education Training Program
  NIH · R25NS099008 · Jul 15, 2017 – Jun 30, 2027 · Role: Principal Investigator
• USC Neurosurgery Research and Education Training Program
  NIH · UE5NS099008 · Jul 15, 2017 – Jun 30, 2027 · Role: Principal Investigator
• Neurotoxicity of Airborne Particles: Role of Chronic Cerebral Hypoperfusion
  NIH · R01ES024936 · Jan 15, 2015 – Nov 30, 2020 · Role: Principal Investigator

• Association of cerebrovascular center volume with patient outcomes. Neurosurg Rev. 2026 Jun 29; 49(1).. View in PubMed
• Impact of intravenous thrombolysis on aspiration thrombectomy outcomes: an Imperative Trial subgroup analysis. J Neurointerv Surg. 2026 May 12.. View in PubMed
• Stroke thrombectomy with a novel reperfusion system including a 0.088” aspiration catheter: the Imperative Trial. J Neurointerv Surg. 2026 Apr 16; 18(5):1202-1209.. View in PubMed
• Cost-Effectiveness of Adjunctive Middle Meningeal Artery Embolization for Chronic Subdural Hematoma: Secondary Analysis of EMBOLISE. AJNR Am J Neuroradiol. 2026 Mar 30.. View in PubMed
• Single cell profiling reveals GSM-15606 attenuates air pollution-induced inflammation and preserves hippocampal neurogenesis. bioRxiv. 2026 Jan 30.. View in PubMed
• National Trends in the Use of Flow Diversion for Management of Intracranial Aneurysms. Neurosurgery. 2026 Jan 08.. View in PubMed
• Induction of ferroptotic and amyloidogenic signatures linked to Alzheimer’s disease by chemically distinct air pollutants. bioRxiv. 2026 Jan 07.. View in PubMed
• Middle Meningeal Artery Embolization for Subdural Hematoma: CT/MRI End Points of the EMBOLISE Trial. Radiology. 2026 01; 318(1):e251746.. View in PubMed
• EMBOLISE randomized surgical trial for subdural hematoma: clinical benefits beyond reoperation with middle meningeal artery embolization. J Neurointerv Surg. 2025 Dec 24.. View in PubMed
• Short-term outcomes and hospitalization cost associated with flow diversion versus coil embolization for unruptured aneurysms: A national assessment. Clin Neurol Neurosurg. 2026 01; 260:109236.. View in PubMed
• Comorbid depression is associated with non-routine discharge following treatment of unruptured cerebral aneurysms. J Clin Neurosci. 2025 Dec; 142:111658.. View in PubMed
• The Role of Diagnostic Spinal Angiography for Thoracoabdominal Aortic Aneurysms: A Clinical Case Series in Patients Undergoing Staged Complex Endovascular Repairs. Neurosurg Pract. 2025 Dec; 6(4):e000167.. View in PubMed
• Clinical outcomes and independently adjudicated results of M2 aspiration thrombectomy: a subgroup analysis from the Imperative Trial. J Neurointerv Surg. 2025 Sep 04.. View in PubMed
• A Bivalent Protease-Activated Receptor-Derived Peptide Mimics Neuronal Anti-Apoptotic Activity of Activated Protein C. Bioengineering (Basel). 2025 Aug 22; 12(9).. View in PubMed
• Semi-automated tortuosity measurements confirm generalizability of IMPERATIVE trial results to real-world patients with acute ischemic stroke undergoing thrombectomy. Interv Neuroradiol. 2025 Jul 21; 15910199251359089.. View in PubMed
• A new era in neurosurgery residency applications: the impact of preference signaling on the neurosurgical match. J Neurosurg. 2025 Oct 01; 143(4):1108-1120.. View in PubMed
• Air pollution decreases postsynaptic PSD-95 and NMDA receptor subunits in synaptosomes from mouse cerebral cortex. Environ Pollut. 2025 Oct 15; 383:126845.. View in PubMed
• The use of generative artificial intelligence-based dictation in a neurosurgical practice: a pilot study. Neurosurg Focus. 2025 07 01; 59(1):E8.. View in PubMed
• Hospital procedural volume is inversely linearly associated with complications in endoscopic endonasal transsphenoidal resection of pituitary tumors. J Neurosurg. 2025 Nov 01; 143(5):1377-1386.. View in PubMed
• The effect of temporary CSF diversion modality on shunt-dependency following aneurysmal subarachnoid hemorrhage: A nationwide assessment. J Clin Neurosci. 2025 Feb; 132:111008.. View in PubMed
• Interleaved flow-sensitive dephasing (iFSD): Toward enhanced blood flow suppression and preserved T1 weighting and overall signals in 3D TSE-based neuroimaging. Magn Reson Med. 2025 May; 93(5):1911-1923.. View in PubMed
• The value of a neurosurgeon: is neurosurgical compensation proportional to value added? A systematic review of the literature and an update on a changing healthcare economy. J Neurosurg. 2025 Apr 01; 142(4):1163-1175.. View in PubMed
• Adjunctive Middle Meningeal Artery Embolization for Subdural Hematoma. N Engl J Med. 2024 Nov 21; 391(20):1890-1900.. View in PubMed
• In vivo neuroprotection in ischemic stroke by activated protein C requires β-arrestin 2. Blood Vessel Thromb Hemost. 2025 Feb; 2(1).. View in PubMed
• Multidisciplinary Approach to Direct Segmental Artery Revascularization to Prevent Spinal Cord Ischemia Associated With Endovascular Thoracoabdominal Aortic Repair. J Endovasc Ther. 2026 Jun; 33(3):1254-1262.. View in PubMed
• Triple Vessel Extracranial-Intracranial Bypass and Distal Clip Occlusion for Giant, Partially Thrombosed Pediatric Fusiform Middle Cerebral Artery Aneurysm: 2-Dimensional Operative Video. Oper Neurosurg. 2024 Nov 04; 29(2):304-305.. View in PubMed
• Design considerations for Factorial Adaptive Multi-Arm Multi-Stage (FAST) clinical trials. Trials. 2024 Sep 12; 25(1):608.. View in PubMed
• Procedural volume is linearly associated with mortality, major complications, and readmissions in patients undergoing malignant brain tumor resection. J Neurooncol. 2024 Nov; 170(2):437-449.. View in PubMed
• Combined endovascular embolization and decompressive craniectomy for microsurgical resection of giant ruptured distal anterior cerebral artery aneurysm. Clin Neurol Neurosurg. 2024 08; 243:108383.. View in PubMed
• Federal and foundational research funding trends for cerebrovascular neurosurgeons: the decline of the cerebrovascular surgeon-scientist? J Neurosurg. 2024 Nov 01; 141(5):1244-1253. Pugazenthi S, Srie . View in PubMed
• Neuroprotection by resveratrol-glucuronide and quercetin-glucuronide via binding to polyphenol- and glycosaminoglycan-binding sites in the laminin receptor. Neural Regen Res. 2025 Mar 01; 20(3):819-820.. View in PubMed
• Corrigendum to ‘Estradiol Protects White Matter of Male C57BL6J Mice against Experimental Chronic Cerebral Hypoperfusion’ [Journal of Stroke and Cerebrovascular Diseases Volume 27, Issue 7, July 2018, Pages 1743-1751]. J Stroke Cerebrovasc Dis. 2024 Jul; 33(7):107710.. View in PubMed
• Direct V3 Vertebral Artery Access for Embolization of Partially Thrombosed Fusiform Basilar Trunk Aneurysm: Technical Case Instruction. Oper Neurosurg. 2024 11 01; 27(5):647-655.. View in PubMed
• Persistent Inequities in Intravenous Thrombolysis for Acute Ischemic Stroke in the United States: Results From the Nationwide Inpatient Sample. J Am Heart Assoc. 2024 05 07; 13(9):e033316.. View in PubMed
• Rates of operative intervention and in-hospital mortality following subarachnoid hemorrhage in patients with COVID-19. J Neurosurg. 2024 Sep 01; 141(3):833-843.. View in PubMed
• Retraction Note: Pericyte degeneration causes white matter dysfunction in the mouse central nervous system. Nat Med. 2024 Apr; 30(4):1215.. View in PubMed
• Cerebral Venous Sinus Thrombosis. Neurosurg Clin N Am. 2024 Jul; 35(3):343-353.. View in PubMed
• Resveratrol and its metabolites elicit neuroprotection via high-affinity binding to the laminin receptor at low nanomolar concentrations. FEBS Lett. 2024 05; 598(9):995-1007.. View in PubMed
• Erratum: “Air Pollution Particulate Matter Exposure and Chronic Cerebral Hypoperfusion and Measures of White Matter Injury in a Murine Model”. Environ Health Perspect. 2024 Feb; 132(2):29001.. View in PubMed
• Microglial TLR4 Mediates White Matter Injury in a Combined Model of Diesel Exhaust Exposure and Cerebral Hypoperfusion. Stroke. 2024 04; 55(4):1090-1093.. View in PubMed
• Subarachnoid Hemorrhage Trials: Cutting, Sliding, or Keeping mRS Scores and WFNS Grades. Stroke. 2024 03; 55(3):779-784.. View in PubMed
• Cyclic adenosine monophosphate-elevating agents inhibit amyloid-beta internalization and neurotoxicity: their action in Alzheimer’s disease prevention. Neural Regen Res. 2023 Dec; 18(12):2675-2676.. View in PubMed
• Association of carotid endarterectomy at low-volume centers with higher likelihood of major complications and nonroutine discharge. J Neurosurg. 2024 05 01; 140(5):1369-1380.. View in PubMed
• Usage of mineralocorticoids and isotonic crystalloids in subarachnoid hemorrhage patients in the United States. J Stroke Cerebrovasc Dis. 2024 Jan; 33(1):107449.. View in PubMed
• Frailty is a Predictor of Increased Readmissions and Increased Postoperative Complications After Elective Treatment of Unruptured Aneurysms. World Neurosurg. 2024 01; 181:e882-e896.. View in PubMed
• Persistent Inequities in Intravenous Thrombolysis for Acute Ischemic Stroke in the United States: Results from the Nationwide Inpatient Sample. medRxiv. 2023 Oct 10.. View in PubMed
• Effect of Air Pollution Particulate Matter on Ischemic and Hemorrhagic Stroke: A Scoping Review. Cureus. 2023 Oct; 15(10):e46694.. View in PubMed
• Subarachnoid Hemorrhage Trials: Cutting, Sliding, or Keeping mRS Scores and WFNS Grades. medRxiv. 2023 Oct 02.. View in PubMed
• Usage of Mineralocorticoids and Isotonic Crystalloids in Subarachnoid Hemorrhage Patients in the United States. medRxiv. 2023 Sep 29.. View in PubMed
• Increased time to surgery and worse perioperative outcome in benign brain tumor patients with COVID-19. J Clin Neurosci. 2023 Nov; 117:20-26.. View in PubMed
• The effect of COVID-19 on treatment and outcomes following ischemic stroke: A national assessment. Clin Neurol Neurosurg. 2023 10; 233:107982.. View in PubMed
• Coronavirus disease-19 is associated with decreased treatment access and worsened outcomes in malignant brain tumor patients. Surg Neurol Int. 2023; 14:292.. View in PubMed
• GPT-4 Artificial Intelligence Model Outperforms ChatGPT, Medical Students, and Neurosurgery Residents on Neurosurgery Written Board-Like Questions. World Neurosurg. 2023 11; 179:e160-e165.. View in PubMed
• Roadmap for Successful Research Training in Neurosurgery. Neurosurgery. 2023 09 01; 93(3):e46-e52.. View in PubMed
• Roadmap for Development of a Strong, Diverse Research Workforce in Neurosurgery. Neurosurgery. 2023 09 01; 93(3):e53-e58.. View in PubMed
• Magnetic resonance imaging of white matter response to diesel exhaust particles. Res Sq. 2023 Jul 18.. View in PubMed
• Endoscopic endonasal approach for MRI-Negative Cushing’s microadenoma. Neurosurg Focus Video. 2023 Jul; 9(1):V5.. View in PubMed
• Myelomeningocele repair at pediatric hospitals: association with routine discharge and shorter hospital stay. J Neurosurg Pediatr. 2023 09 01; 32(3):376-383.. View in PubMed
• Pediatric patients with malignant brain tumor treated at children’s hospitals: association with fewer unplanned readmissions. J Neurosurg Pediatr. 2023 09 01; 32(3):324-331.. View in PubMed
• Carotid artery stenting for asymptomatic stenosis is associated with decreased 30-day readmission at very high volume centers. J Clin Neurosci. 2023 Aug; 114:1-8.. View in PubMed
• Flavonoid quercetin and its glucuronide and sulfate conjugates bind to 67-kDa laminin receptor and prevent neuronal cell death induced by serum starvation. Biochem Biophys Res Commun. 2023 09 03; 671:116-123.. View in PubMed
• Anatomic Considerations Guiding Single Versus Multiportal Endoscopic Approaches for Resection of Juvenile Nasopharyngeal Angiofibroma: Cases Series With Graded Multicorridor Resections. Oper Neurosurg. 2023 08 01; 25(2):150-160.. View in PubMed
• Mortality following mechanical thrombectomy for ischemic stroke in patients with COVID-19. J Stroke Cerebrovasc Dis. 2023 Aug; 32(8):107171.. View in PubMed
• Combined open revascularization and endovascular treatment of complex intracranial aneurysms: case series. Front Neurol. 2023; 14:1102496.. View in PubMed
• Endovascular Embolization of Intracranial Meningiomas. Neurosurg Clin N Am. 2023 Jul; 34(3):371-380.. View in PubMed
• ChatGPT versus the neurosurgical written boards: a comparative analysis of artificial intelligence/machine learning performance on neurosurgical board-style questions. J Neurosurg. 2023 03 24; 139(3):904-911.. View in PubMed
• Making a case for endovascular approaches for neural recording and stimulation. J Neural Eng. 2023 01 25; 20(1).. View in PubMed
• Stimulating neurosurgery department research via goal-directed research training of residents. J Neurosurg. 2023 05 01; 138(5):1478-1481.. View in PubMed
• Particulate matter exposure and chronic cerebral hypoperfusion promote oxidative stress and induce neuronal and oligodendrocyte apoptosis in male mice. J Neurosci Res. 2023 03; 101(3):384-402.. View in PubMed
• Interhospital transfer of pediatric patients with malignant brain tumor not associated with increased mortality, but safe routine discharge. J Neurosurg Pediatr. 2023 02 01; 31(2):124-131.. View in PubMed
• cAMP-induced decrease in cell-surface laminin receptor and cellular prion protein attenuates amyloid-β uptake and amyloid-β-induced neuronal cell death. FEBS Lett. 2022 11; 596(22):2914-2927.. View in PubMed
• Getting ahead of stroke. J Neurointerv Surg. 2022 08; 14(8):743-744.. View in PubMed
• Interhospital transfer of patients with malignant brain tumors undergoing resection is associated with routine discharge. Clin Neurol Neurosurg. 2022 10; 221:107372.. View in PubMed
• 2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2022 07; 53(7):e282-e361.. View in PubMed
• Neurotoxicity of Diesel Exhaust Particles. J Alzheimers Dis. 2022; 89(4):1263-1278.. View in PubMed
• Nogo-A receptor internalization by cyclic adenosine monophosphate in overcoming axonal growth inhibitors after stroke. Neural Regen Res. 2022 Jan; 17(1):91-92.. View in PubMed
• Disparities in the Surgical Treatment of Cerebrovascular Pathologies: A Contemporary Systematic Review. World Neurosurg. 2022 02; 158:244-257.e1.. View in PubMed
• Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology and Demyelination Caused by Hypoperfusion. Front Immunol. 2021; 12:785519.. View in PubMed
• Minocycline decreases blood-brain barrier permeability following aneurysmal subarachnoid hemorrhage: a randomized, double-blind, controlled trial. J Neurosurg. 2022 May 01; 136(5):1251-1259.. View in PubMed
• Disparities in the Surgical Treatment of Adult Spine Diseases: A Systematic Review. World Neurosurg. 2022 02; 158:290-304.e1.. View in PubMed
• Air Pollution Particulate Matter Exposure and Chronic Cerebral Hypoperfusion and Measures of White Matter Injury in a Murine Model. Environ Health Perspect. 2021 08; 129(8):87006.. View in PubMed
• Readmissions after ventricular shunting in pediatric patients with hydrocephalus: a Nationwide Readmissions Database analysis. J Neurosurg Pediatr. 2021 11 01; 28(5):553-562.. View in PubMed
• Middle Cerebral Artery Thrombectomy: Clinical Findings and Technical Pearls: 2-Dimensional Operative Video. Oper Neurosurg. 2021 07 15; 21(2):E107-E108.. View in PubMed
• Nanoparticulate matter exposure results in white matter damage and an inflammatory microglial response in an experimental murine model. PLoS One. 2021; 16(7):e0253766.. View in PubMed
• Transcranial eddy current damping sensors for detection and imaging of hemorrhagic stroke: feasibility in benchtop experimentation. Neurosurg Focus. 2021 07; 51(1):E15.. View in PubMed
• A systematic review of next-generation point-of-care stroke diagnostic technologies. Neurosurg Focus. 2021 07; 51(1):E11.. View in PubMed
• Evaluating Medicaid expansion benefits for patients with cancer: National Cancer Database analysis and systematic review. J Cancer Policy. 2021 09; 29:100292.. View in PubMed
• Hospital Admissions from the Emergency Department and Subsequent Critical Care Interventions for Influenza during Pregnancy. Am J Perinatol. 2023 02; 40(3):326-332.. View in PubMed
• Global impact of COVID-19 on stroke care. Int J Stroke. 2021 07; 16(5):573-584.. View in PubMed
• Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic. Stroke Vasc Neurol. 2021 12; 6(4):542-552.. View in PubMed
• Investigating the blood-spinal cord barrier in preclinical models: a systematic review of in vivo imaging techniques. Spinal Cord. 2021 Jun; 59(6):596-612.. View in PubMed
• Comorbid depression in surgical cancer patients associated with non-routine discharge and readmission. Surg Oncol. 2021 Jun; 37:101533.. View in PubMed
• Tracking Scan to Incision Time in Patients with Emergent Operative Traumatic Brain Injuries as a Measure for Systems-Based Practice in Neurosurgical Trainees. World Neurosurg. 2021 05; 149:e491-e497.. View in PubMed
• Neuroprotective effect of minocycline against acute brain injury in clinical practice: A systematic review. J Clin Neurosci. 2021 Apr; 86:50-57.. View in PubMed
• Letter to the Editor. Scoring change for Step 1 of the United States Medical Licensing Examination. J Neurosurg. 2021 06 01; 134(6):2012-2013.. View in PubMed
• Increasing Prevalence of Frailty and Its Association with Readmission and Mortality Among Hospitalized Patients with IBD. Dig Dis Sci. 2021 12; 66(12):4178-4190.. View in PubMed
• Urban Air Pollution Nanoparticles from Los Angeles: Recently Decreased Neurotoxicity. J Alzheimers Dis. 2021; 82(1):307-316.. View in PubMed
• Strategies for writing a successful National Institutes of Health grant proposal for the early-career neurointerventionalist. J Neurointerv Surg. 2020 Nov 25.. View in PubMed
• National Institutes of Health grant opportunities for the neurointerventionalist: preparation and choosing the right mechanism. J Neurointerv Surg. 2020 Nov 25.. View in PubMed
• Tobacco Use Is Associated with Readmission within 90 Days after Craniotomy. Clin Neurol Neurosurg. 2021 01; 200:106383.. View in PubMed