Computational and Mathematical Methods in Medicine

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American Heart Association Council on cardiovascular nursing.

Turning blood into brain: Cells bearing neuronal antigens generated in vivo from bone marrow

Various lines of evidence suggest that immune system dysregulation has a key role in autism spectrum disorder (ASD). Estes and McAllister review this evidence, covering genetic and maternal immune system-related risk factors, chronic immune system changes in individuals with ASD and in animal models, and potential pathophysiological mechanisms. Increasing evidence points to a central role for immune dysregulation in autism spectrum disorder (ASD). Several ASD risk genes encode components of the immune system and many maternal immune system-related risk factors — including autoimmunity, infection and fetal reactive antibodies — are associated with ASD. In addition, there is evidence of ongoing immune dysregulation in individuals with ASD and in animal models of this disorder. Recently, several molecular signalling pathways — including pathways downstream of cytokines, the receptor MET, major histocompatibility complex class I molecules, microglia and complement factors — have been identified that link immune activation to ASD phenotypes. Together, these findings indicate that the immune system is a point of convergence for multiple ASD-related genetic and environmental risk factors.

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Immune mediators in the brain and peripheral tissues in autism spectrum disorder

Cellular Therapy Targeting Functional Outcome in a Case of Cervical Spinal Cord Injury

Aims: Cerebral palsy (CP) is an umbrella term including a group of permanent disorders of development of movement and of posture causing activity limitation. Oxidative stress and glutamate mediated excitotoxicity are important mechanisms of injury to both the white matter and neurons in the developing brain resulting in motor deficits. No treatment measures are available that can repair the existing damage. Use of bone marrow stem cells for the treatment of CP has shown promise owing to their capacity for self-renewal, differentiation with a potential of neuroregeneration and secretory paracrine effects. Methods: To study the efficacy of cell transplantation in CP, we administered autologous bone marrow mononuclear cells intrathecally to a 2.2-year-old female patient. She was followed up at 9 months and a repeat transplantation was administered. A second follow up was done 5 months after second transplantation. Gross Motor Function Classification System-Expanded & Revised (GMFCS-E&R), Gross Motor Function Measure-88 (GMFM-88) and Functional Independence Measure for children (WeeFIM) were used as outcome measures to assess therapeutic efficacy. Results: 9 months after first transplantation, symptomatic improvements such as reduced spasticity, ability to crawl with reciprocal pattern, independent walking with walker, independent transfer from bed to floor, improved biting and chewing and cognition were observed. On GMFCS-E&R she improved from level III to level II, GMFM-88 improved from 36.36% to 38.62% and WeeFIM improved from 34 to 38. These improvements were well supported by positron emission tomography–computed tomography which showed improved metabolism in bilateral cerebellum and medial temporal cortex. All these improvements were maintained even at 5 months’ follow up post second transplantation. No adverse events were reported after the procedures or at follow ups. Conclusion: Intrathecal administration of autologous bone marrow mononuclear cells are safe and an effective therapeutic strategy in the management of CP.

Clinical translation of the benefits of cell transplantation in a case of cerebral palsy

Background: Cerebral palsy (CP) is a non-progressive disorder. The global incidence of neonatal CP is 1-5 per 1000 live births where 45% of children with CP have a comorbid intellectual disability (ID). This affects the quality of life and reduces life expectancy of affected individuals.
Methods and findings: With an aim to study the efficacy and safety of autologous bone marrow mononuclear cells (BMMNCs) transplantation in CP with ID, we administered a 17-year-old boy with BMMNCs along with neurorehabilitation. On follow up after 6 months, clinical improvements were recorded in speech, fine motor skills, ambulation, oromotor skills, social awareness, cognitive skills, memory and attention. Comparative Positron Emission Tomography- Computer Tomography scan of brain before and six months after cell transplantation revealed improved metabolism in the anterior cingulate cortex, left caudate head, thalamus, medial temporal cortex, cerebellum. Intelligent Quotient improved from 21 to 29. Social age according to the Vineland Social Maturity Scale was increased by 1 year. Functional Independence Measure and Gross Motor Functional Measure increased from 22 to 26 and 74.65 to 76 respectively. On Gross Motor Functional Classification System, he improved from IV to III.
Conclusion: These changes suggest that BMMNCs transplantation along with neurorehabilitation was effective for this child suffering from CP with ID.
Keywords
Cerebral palsy; Intellectual disability; Autologous bone marrow mononuclear cells; Cell transplantation; Positron emission tomography-computer tomography

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Prerna Badhe

Papers

Cellular Therapy Targeting Functional Outcome in a Case of Cervical Spinal Cord Injury

Clinical translation of the benefits of cell transplantation in a case of cerebral palsy

Cell Transplantation: A Novel Therapeutic Modality for Cerebral Palsy with Co-Morbid Intellectual Disability