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Plasma Derived From Human Umbilical Cord Blood: Potential Cell-Additive Or Cell-Substitute Therapeutic For Neurodegenerative Diseases, Jared Ehrhart, Paul R. Sanberg, Svitlana Garbuzova-Davis 2018 Saneron CCEL Therapeutics

Plasma Derived From Human Umbilical Cord Blood: Potential Cell-Additive Or Cell-Substitute Therapeutic For Neurodegenerative Diseases, Jared Ehrhart, Paul R. Sanberg, Svitlana Garbuzova-Davis

Neurosurgery and Brain Repair Faculty Publications

Limited efficacy of current therapeutic approaches for neurodegenerative disease has led to increased interest in alternative therapies. Cord blood plasma (CBP) derived from human umbilical cord blood (hUCB) may be a potential therapeutic. Benefits of CBP injection into rodent models of aging or ischaemic stroke have been demonstrated, though how benefits are elicited is still unclear. The present study evaluated various factors within the same samples of CBP and human adult blood plasma/sera (ABP/S). Also, autologous CBP effects vs. ABP/S or foetal bovine serum supplements on mononuclear cells from hUCB (MNC hUCB) in vitro were determined. Results showed significantly low …


Reduction Of Microhemorrhages In The Spinal Cord Of Symptomatic Als Mice After Intravenous Human Bone Marrow Stem Cell Transplantation Accompanies Repair Of The Blood-Spinal Cord Barrier, David J. Eve, George Steiner, Ajay Mahendrasah, Paul R. Sanberg, Crupa Kurien, Avery Thomson, Cesar V. Borlongan, Svitlana Garbuzova-Davis 2018 University of South Florida

Reduction Of Microhemorrhages In The Spinal Cord Of Symptomatic Als Mice After Intravenous Human Bone Marrow Stem Cell Transplantation Accompanies Repair Of The Blood-Spinal Cord Barrier, David J. Eve, George Steiner, Ajay Mahendrasah, Paul R. Sanberg, Crupa Kurien, Avery Thomson, Cesar V. Borlongan, Svitlana Garbuzova-Davis

Neurosurgery and Brain Repair Faculty Publications

Blood-spinal cord barrier (BSCB) alterations, including capillary rupture, have been demonstrated in animal models of amyotrophic lateral sclerosis (ALS) and ALS patients. To date, treatment to restore BSCB in ALS is underexplored. Here, we evaluated whether intravenous transplantation of human bone marrow CD34+ (hBM34+) cells into symptomatic ALS mice leads to restoration of capillary integrity in the spinal cord as determined by detection of microhemorrhages. Three different doses of hBM34+ cells (5 × 104, 5 × 105 or 1 × 106) or media were intravenously injected into symptomatic G93A SOD1 mice …


Human Umbilical Cord Blood Serum–Derived Α-Secretase: Functional Testing In Alzheimer’S Disease Mouse Models, Ahsan Habib, Huayan Hou, Takashi Mori, Jun Tian, Jin Zeng, Shengnuo Fan, Brian Giunta, Paul R. Sanberg, Darrell Sawmiller, Jun Tan 2018 University of South Florida

Human Umbilical Cord Blood Serum–Derived Α-Secretase: Functional Testing In Alzheimer’S Disease Mouse Models, Ahsan Habib, Huayan Hou, Takashi Mori, Jun Tian, Jin Zeng, Shengnuo Fan, Brian Giunta, Paul R. Sanberg, Darrell Sawmiller, Jun Tan

Neurosurgery and Brain Repair Faculty Publications

Alzheimer’s disease (AD) is an age-related disorder that affects cognition. Our previous studies showed that the neuroprotective fragment of amyloid procurer protein (APP) metabolite, soluble APPα (sAPPα), interferes with β-site APP-cleaving enzyme 1 (BACE1, β-secretase) cleavage and reduces amyloid-β (Aβ) generation. In an attempt to identify approaches to restore sAPPα levels, we found that human cord blood serum (CBS) significantly promotes sAPPα production compared with adult blood serum (ABS) and aged blood serum (AgBS) in Chinese hamster ovary cells stably expressing wild-type human APP. Interestingly, CBS selectively mediated the α-secretase cleavage of human neuron-specific recombinant APP695 in a cell-free …


Therapeutic Cocktail Approach For Treatment Of Hyperhomocysteinemia In Alzheimer’S Disease, Michael Leon, Darrell Sawmiller, R. Douglas Shytle, Jun Tan 2018 University of South Florida

Therapeutic Cocktail Approach For Treatment Of Hyperhomocysteinemia In Alzheimer’S Disease, Michael Leon, Darrell Sawmiller, R. Douglas Shytle, Jun Tan

Neurosurgery and Brain Repair Faculty Publications

In the United States, Alzheimer's disease (AD) is the most common cause of dementia, accompanied by substantial economic and emotional costs. During 2015, more than 15 million family members who provided care to AD patients had an estimated total cost of 221 billion dollars. Recent studies have shown that elevated total plasma levels of homocysteine (tHcy), a condition known as hyperhomocysteinemia (HHcy), is a risk factor for AD. HHcy is associated with cognitive decline, brain atrophy, and dementia; enhances the vulnerability of neurons to oxidative injury; and damages the blood–brain barrier. Many therapeutic supplements containing vitamin B12 and folate have …


Progress And Updates In Stroke Research: Introduction To The Special Issue On Stroke, Yu Luo, John H. Zhang, Paul R. Sanberg, Samantha M. Portis 2018 University of Cincinnati

Progress And Updates In Stroke Research: Introduction To The Special Issue On Stroke, Yu Luo, John H. Zhang, Paul R. Sanberg, Samantha M. Portis

Neurosurgery and Brain Repair Faculty Publications

As guest editors of this special issue, we are delighted to present 13 articles that discuss advances in stroke research including translational stroke research, stroke research milestones, and proposals for future directions. Stroke is a major cause of disability, and, according to the Centers for Disease Control and Prevention, is the fifth leading cause of death in the US alone. Possible factors contributing to stroke pathogenesis are elucidated and possible treatment modalities are explored in the following special issue of Cell Transplantation.


Human Cord Blood Serum-Derived App Α-Secretase Cleavage Activity Is Mediated By C1 Complement, Ahsan Habib, Darrell Sawmiller, Huayan Hou, Manasa Kanithi, Jun Tian, Jin Zeng, Dan Zi, Zhi-Xu He, Paul R. Sanberg, Jun Tan 2018 University of South Florida

Human Cord Blood Serum-Derived App Α-Secretase Cleavage Activity Is Mediated By C1 Complement, Ahsan Habib, Darrell Sawmiller, Huayan Hou, Manasa Kanithi, Jun Tian, Jin Zeng, Dan Zi, Zhi-Xu He, Paul R. Sanberg, Jun Tan

Neurosurgery and Brain Repair Faculty Publications

Alzheimer’s Disease (AD) is the leading cause of dementia in the elderly. In healthy individuals, amyloid precursor protein (APP) is cleaved by α-secretase, generating soluble α-amyloid precursor protein (sAPPα), which contributes neuroprotective functions in the neuronal environment. In contrast, in the neurodegenerative environment of AD patients, amyloid-β-peptide (Aβ) of either 40 or 42 residues are generated by increased activity of β- and γ-secretase. These proteins amalgamate in specific regions of the brain, which disrupts neuronal functions and leads to cognitive impairment. Human umbilical cord blood cells (HUCBC) have proven useful as potential immunomodulatory therapies in various models of neurodegenerative diseases, …


Wada Asymmetry In Patients With Drug-Resistant Mesial Temporal Lobe Epilepsy: Implications For Postoperative Neuropsychological Outcomes, Ryan W. Sever, Andrew C. Vivas, Fernando L. Vale, Mike R. Schoenberg 2018 University of South Florida

Wada Asymmetry In Patients With Drug-Resistant Mesial Temporal Lobe Epilepsy: Implications For Postoperative Neuropsychological Outcomes, Ryan W. Sever, Andrew C. Vivas, Fernando L. Vale, Mike R. Schoenberg

Neurosurgery and Brain Repair Faculty Publications

No abstract provided.


Intra-Arterial Nitroglycerin As Directed Acute Treatment In Experimental Ischemic Stroke, Michael E. Maniskas, Jill M. Roberts, Rebecca Trueman, Annastazia E. Learoyd, Amanda A. Gorman, Justin F. Fraser, Gregory J. Bix 2018 University of Kentucky

Intra-Arterial Nitroglycerin As Directed Acute Treatment In Experimental Ischemic Stroke, Michael E. Maniskas, Jill M. Roberts, Rebecca Trueman, Annastazia E. Learoyd, Amanda A. Gorman, Justin F. Fraser, Gregory J. Bix

Neuroscience Faculty Publications

BACKGROUND: Nitroglycerin (also known as glyceryl trinitrate (GTN)), a vasodilator best known for treatment of ischemic heart disease, has also been investigated for its potential therapeutic benefit in ischemic stroke. The completed Efficacy of Nitric Oxide in Stroke trial suggested that GTN has therapeutic benefit with acute (within 6 hours) transdermal systemic sustained release therapy.

OBJECTIVE: To examine an alternative use of GTN as an acute therapy for ischemic stroke following successful recanalization.

METHODS: We administered GTN IA following transient middle cerebral artery occlusion in mice. Because no standard dose of GTN is available following emergent large vessel occlusion, we …


Survival Benefit Of Surgery In Recurrent Glioblastoma Multiforme, Usama Khalid Choudry, Saad Akhtar Khan, Muhammad Shahzad Shamim 2017 Aga Khan University

Survival Benefit Of Surgery In Recurrent Glioblastoma Multiforme, Usama Khalid Choudry, Saad Akhtar Khan, Muhammad Shahzad Shamim

Section of Neurosurgery

There is an ongoing debate regarding role of surgery for recurrent glioblastoma multiforme (GBM). Older literature hinted at only modest survival benefits with surgery and a high rate of morbidity. However, more recent literature suggests better survival that may be attributed to better surgical techniques and better options in adjuvant treatment. Herein the authors review recent literature with regards to the possible role of surgery in recurrent GBM and also look into the key factors impacting second surgery.


Anaesthetic Management Of Supratentorial Tumor Craniotomy Using Awake-Throughout Approach, Faraz Shafiq, Fahad Salim, Ather Enam, Jai Parkash, Mohammad Faheem 2017 Aga Khan University

Anaesthetic Management Of Supratentorial Tumor Craniotomy Using Awake-Throughout Approach, Faraz Shafiq, Fahad Salim, Ather Enam, Jai Parkash, Mohammad Faheem

Department of Anaesthesia

The authors are reporting an anaesthetic management of patient presenting with left parietal lobe space occupying lesion and scheduled for Awake-craniotomy. Awake-throughout approach using scalp block was planned. Among techniques reported for keeping patient awake during the surgery, this one is really underutilized. The successful conduct requires thorough preoperative assessment and psychological preparation. We used powerpoint presentation as a preoperative teaching tool. The anatomical landmark technique was used to institute scalp block, where individual nerves were targeted bilaterally. Patient remained stable throughout and participated actively in intraoperative neurological monitoring. Postoperative period showed remarkable recovery, better pain control, and shorter length …


Reading Between The Joints-Using Spinal Magnetic Resonance Imaging For Evaluation Of Instability, Komal Naeem, S. Ather Enam 2017 Aga Khan University

Reading Between The Joints-Using Spinal Magnetic Resonance Imaging For Evaluation Of Instability, Komal Naeem, S. Ather Enam

Section of Neurosurgery

No abstract provided.


Comparison Between Endoscopic And Microscopic Approaches For Surgery Of Pituitary Tumours, Inamullah Khan, Muhammad Shahzad Shamim 2017 Aga Khan University

Comparison Between Endoscopic And Microscopic Approaches For Surgery Of Pituitary Tumours, Inamullah Khan, Muhammad Shahzad Shamim

Section of Neurosurgery

Surgical techniques for resection of pituitary tumours have come a long way since it was first introduced in late 18th century. Nowadays, most pituitary surgeries are performed through trans-nasal trans-sphenoidal approach either using a microscope, or an endoscope. Herein the authors review the literature and compare these two instruments with regards to their outcomes when used for resection of pituitary tumours. .


Flipped Classroom Instructional Approach In Undergraduate Medical Education, Syeda Sadia Fatima, Fazal Manzoor Arain, Ather Enam 2017 Aga Khan University

Flipped Classroom Instructional Approach In Undergraduate Medical Education, Syeda Sadia Fatima, Fazal Manzoor Arain, Ather Enam

Department of Biological & Biomedical Sciences

Objective: In this study we implemented the “flipped classroom” model to enhance active learning in medical students taking neurosciences module at Aga Khan University, Karachi.
Methods: Ninety eight undergraduate medical students participated in this study. The study was conducted from January till March 2017. Study material was provided to students in form of video lecture and reading material for the non-face to face sitting, while face to face time was spent on activities such as case solving, group discussions, and quizzes to consolidate learning under the supervision of faculty. To ensure deeper learning, we used pre- and post-class …


Delayed Spinal Cord Infarction Following Anterior Cervical Surgical Decompression, Muhammad Faheem Khan, Rashid Jooma, Fauzan Alam Hashmi, Muhammad Faraz Raghib 2017 Aga Khan University

Delayed Spinal Cord Infarction Following Anterior Cervical Surgical Decompression, Muhammad Faheem Khan, Rashid Jooma, Fauzan Alam Hashmi, Muhammad Faraz Raghib

Section of Neurosurgery

Anterior cervical discectomy and fusion (ACDF) for cord compression is a safe and effective procedure with good outcomes. However, worsening of myelopathy is the most feared adverse event of the surgery. We report the case of a 36-year-old male patient who presented with an acute non-traumatic C5-6 cervical disc herniation causing incomplete quadriparesis. He underwent an uncomplicated ACDF at C5-6, and after an initial period of improvement, he developed a delayed onset of an anterior cord syndrome on day 3, without any discerning cause. We have reviewed similar cases reported in the literature and believe that our patient's postsurgical course …


Role Of 5-Ala In Improving Extent Of Tumour Resection In Patients With Glioblastoma Multiforme, Muhammad Waqas, Inamullah Khan, Muhammad Shahzad Shamim 2017 Aga Khan University

Role Of 5-Ala In Improving Extent Of Tumour Resection In Patients With Glioblastoma Multiforme, Muhammad Waqas, Inamullah Khan, Muhammad Shahzad Shamim

Section of Neurosurgery

Goal of surgery for patients with Glioblastoma Multiforme (GBM) is gross total resection with no new neurological deficits. Surgical resection is often restricted due the difficulty in differentiating the tumour from surrounding normal brain using either naked eye, or standard intra-operative white light microscopy. GBM uptakes orally administered 5-ALA becomes fluorescent when viewed by a special light, and this property has been used to improve intra-operative tumour identification. This technique should therefore allow better extent of tumour resection. The hypothesis has been tested through several studies and even though most studies are of low quality, they strongly favour the use …


Video Microscope Robotic Arm-Assisted, Neuronavigation-Guided Glioma Resection And Regional Sampling, Muhammad Waqas, Ather Enam, Fauzan A Hashmi, Fatima Mubarak, Fazal Arain 2017 Aga Khan University

Video Microscope Robotic Arm-Assisted, Neuronavigation-Guided Glioma Resection And Regional Sampling, Muhammad Waqas, Ather Enam, Fauzan A Hashmi, Fatima Mubarak, Fazal Arain

Section of Neurosurgery

High-grade gliomas possess internal pathological heterogeneity. Selective sampling of different tumor regions can help in the study of this heterogeneity. In this report, we have described the use of a novel navigation and optical system for the selective regional sampling of a high-grade glioma lesion. A 45-year-old gentleman presented to us with complaints of intermittent frontal headaches for past eight months. On examination, he had subtle pyramidal weakness in left upper and lower extremities. Magnetic resonance imaging (MRI) showed a large contrast-enhancing, space-occupying lesion in the right frontal lobe causing perilesional edema and midline shift. We marked four different regions …


Mini-Craniotomy Under Local Anesthesia For Chronic Subdural Hematoma: An Effective Choice For Elderly Patients And For Patients In A Resource-Strained Environment, Shaikh Danish Mahmood, Muhammad Waqas, Mirza Zain Baig, Aneela Darbar 2017 Aga Khan University

Mini-Craniotomy Under Local Anesthesia For Chronic Subdural Hematoma: An Effective Choice For Elderly Patients And For Patients In A Resource-Strained Environment, Shaikh Danish Mahmood, Muhammad Waqas, Mirza Zain Baig, Aneela Darbar

Medical College Documents

Background: Mini-craniotomy for chronic subdural hematoma (CSDH) is associated with lower rates of recurrence. However, the procedure is performed mostly with the patient under general anesthesia (GA) and therefore frequently requires an intensive care unit (ICU) facility, especially in the elderly population. Because of the unavailability of ICU beds, and to avoid GA, we started to perform this procedure with the patient under local anesthesia (LA).
Materials and methods: This was a retrospective medical chart review conducted in the section of Neurosurgery at the Aga Khan Hospital in Karachi, Pakistan. The study duration was 1 year. We included patients aged …


Diffusion Tensor Imaging For Ruptured Cerebral Arteriovenous Malformation, Muhammad Waqas, Ayesha Siddiqui, Fatima Mubarak, Ather Enam 2017 Aga Khan University

Diffusion Tensor Imaging For Ruptured Cerebral Arteriovenous Malformation, Muhammad Waqas, Ayesha Siddiqui, Fatima Mubarak, Ather Enam

Section of Neurosurgery

Non-ruptured arteriovenous malformations (AVMs) rarely cause tract disruption. Few studies have described how ruptured AVMs influence white matter (WM) tract morphology. We reviewed consecutive AVM cases treated at a tertiary care hospital where diffusion tensor imaging (DTI) tractography was obtained preoperatively. DTI was performed using the Synaptive Plan (Synaptive Medical Inc., Toronto, Canada). Quality control was performed by clinical application specialist. Perinidal fractional anisotropy (FA) value of corticospinal tracts (CST) was obtained. A reference FA value was obtained from the corresponding area on the contralateral side. Images were evaluated by a consultant neuroradiologist. Radiological findings were correlated with clinical findings. …


Self‑Resolving Prepontine Cyst, Muhammad Waqas, Inamullah Khan, Reehana Khawaja, Ayesha Quddusi, Ather Enam 2017 Aga Khan University

Self‑Resolving Prepontine Cyst, Muhammad Waqas, Inamullah Khan, Reehana Khawaja, Ayesha Quddusi, Ather Enam

Section of Neurosurgery

Background: Intracranial prepontine cysts are rare and include epidermoid cysts, arachnoid cysts, and neurenteric cysts. Symptomatic prepontine cysts may require surgical intervention. Reports of spontaneous resolution of cysts are rare.
Case description: We describe the case of a young gentleman who presented with headache and fever. Magnetic resonance imaging of the brain identified a prepontine lesion with features consistent with epidermoid cyst. During admission, the patient received symptomatic management in addition to empirical antibiotic therapy and dexamethasone. The patient improved symptomatically in the next 48 hours and was discharged. Follow-up imaging at 6 months and 1 year showed significant reduction …


Ruptured Mycotic Aneurysms: Report And Outcomes Of Two Surgically Managed Patients, Aleena Khan, Muhammad Waqas, Waseem Mehmood Nizamani, Muhammad Ehsan Bari 2017 Aga Khan University

Ruptured Mycotic Aneurysms: Report And Outcomes Of Two Surgically Managed Patients, Aleena Khan, Muhammad Waqas, Waseem Mehmood Nizamani, Muhammad Ehsan Bari

Section of Neurosurgery

Background: Mycotic aneurysm is a rare potentially life-threatening complication of infective endocarditis (IE). Little data is available on the management and outcomes of ruptured mycotic aneurysms with large intracerebral hematoma. Few cases have been described on the management of mycotic aneurysm in the presence of life-threatening hematoma and mass effect.
Case description: We are presenting two cases of ruptured mycotic aneurysm with intracerebral hematoma and impending brain herniation. Both patients had signs of high intracranial pressure and required urgent surgical evacuation of clot. One patient survived while the other patient expired soon after surgery.
Conclusion: Mycotic aneurysm of middle cerebral …


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