University of Rochester

Cornell University

New York Medical College

Other

The State University of New York

Maiken Nedergaard

Steven A Goldman

Rashid Deane

Humberto Mestre Payne

Helene Benveniste

Vinita Rangroo Thrane

Benjamin Plog

Alexander Stanley Thrane

Jeffrey J Iliff

Jane Lin

Alexander Thrane

This invention relates to improving delivery of agents to the central nervous system.

Glymphatic delivery by manipulating plasma osmolarity

The present disclosure is directed to a method of treating a neuropsychiatric disorder. This method involves selecting a subject having the neuropsychiatric disorder and administering to the selected subject a preparation of glial progenitor cells at a dosage effective to treat the neuropsychiatric disorder in the subject. Another aspect of the disclosure is directed to a method of treating a neuropsychiatric disorder that includes selecting a subject having the neuropsychiatric disorder and administering, to the selected subject, a potassium (K) channel activator at a dosage effective to restore normal brain interstitial glial Klevels in the selected subject and treat the neuropsychiatric disorder is also disclosed.

Methods of treating neuropsychiatric disorders

Methods are provided for measuring glio-vascular pathway ('glymphatic system') function in the brain of a mammal which include performing imaging of the brain and measuring cerebrospinal fluid-interstitial fluid (CSF-ISF) exchange in the brain. The methods can be used to track the exchange between CSF and ISF compartments. An imaging agent is optionally administered intrathecally. The imaging agent can be a negative or positive (paramagnetic) contrast agent and dynamic or contrast-enhanced magnetic resonance imaging (MRI) of the brain can be performed. The imaging agent can be a positron-emitting radionuclide tracer and positron emission tomography (PET) can be performed. Methods for treating diseases or disorders of the mammalian brain are also provided, in which the methods increase or decrease glymphatic clearance.

Methods for evaluating brain-wide paravascular pathway for waste clearance function and methods for treating neurodegenerative disorders based thereon

The disclosure relates to a method of treating and/or preventing brain impairment in a subject that has or is susceptible to ammonia neurotoxicity (increased plasma ammonia), by administering a Na-; &#x2014;K+-2CI- cotransporter isoform 1 ('NKCC1') inhibitor to the selected subject under conditions effective to treat and/or prevent brain impairment. The disclosure further relates to methods of maintaining the fundamental function of astrocytic potassium buffering and inhibiting accumulation of potassium star rounding astrocytes, both of which involve contacting astrocytes with a NKCC 1 inhibitor.

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The present invention is directed to a method of treating a subject with acute spinal cord injury by administering a purine receptor antagonist to the subject under conditions effective to treat spinal cord injury. The purine receptor antagonist inhibits P2X purine receptor activation. The inhibition of P2X purine receptor activation can also be used in conjunction with methods of treating a subject with spinal cord ischemia resulting from stroke or vascular insult, interruption, or mechanical injury, treating a subject with ischemic or traumatic insults of brain tissue in regions expressing P2X receptors, and for inhibiting ATP-triggered brain or spinal cord cell death.

Purine receptor inhibition as a therapeutic strategy in spinal cord and brain

The present invention relates to a method of inhibiting differentiation of a population of neural stem cells by contacting a purinergic receptor agonist and a population of neural stem cells under conditions effective to inhibit differentiation of the population of neural stem cells. Another aspect of the present invention relates to a method of producing neurons and/or glial cells from a population of neural stem cells by culturing a population of neural stem cells with a purinergic receptor antagonist under conditions effective to cause the neural stem cells to differentiate into neurons and/or glial cells. The purinergic receptor agonist can also be used in a method of inducing proliferation and self-renewal of neural stem cells in a subject and a method of treating a neurological disease or neurodegenerative condition in a subject. The purinergic receptor antagonist can also be used in treating a neoplastic disease of the brain or spinal cord in a subject.

Purines are self-renewal signals for neural stem cells, and purine receptor antagonists promote neuronal and glial differentiation therefrom

The present invention relates to a method of treating glial tumors in a subject, which includes providing a glutamate antagonist or a NMDA receptor antagonist and administering the glutamate antagonist or NMDA receptor antagonist to a subject with a glial tumor of the brain or spinal cord under conditions effective to treat the glial tumor.

Treatment of glial tumors with glutamate antagonists

The present invention provides neuronal progenitor cells which have been identified in histological sections of the adult human brain. The present invention also provides methods to localize, characterize, harvest, and propagate neuronal progenitor cells derived from human brain tissue. Additional methods are provided for introducing and expressing genes in the brain.

Discovery, localization, harvest, and propagation of an FGF2 and BDNF-responsive population of neural and neuronal progenitor cells in the adult human forebrain

Growing community of inventors

Webster, NY, United States of America

Maiken Nedergaard