Protein kinase c gamma as a biomarker for neuropsychological and cognitive functions in the central nervous system

Abstract

Embodiments of the present invention are directed to a biological marker, the gamma isoform of protein kinase C (PKCg), which surprisingly allows rapid identification of compromised cognitive, behavioral, and neuropsychological functions under conditions associated with acute, transient hypoxia in humans. It was surprisingly discovered that PKCg is released from neural cells and can be detected in peripheral blood after hypoxic events unrelated to the reduction or elimination of blood flow through affected tissues. Embodiments of this invention are also directed to a broad range of clinical applications, particularly in emergency medicine. Other embodiments are related to compositions and methods for distinguishing between hypoxic encephalopathies and conditions arising from neuroanatomical/structural anomalies and/or incidental pathologies, for example, alcohol intoxication.

1 - 13 . (canceled) 
     
     
         14 . A method for assessing the potential for impairment of a neuropsychological or cognitive function of the central nervous system of a patient comprising: contacting a sample obtained from the patient with a binding partner capable of forming a binding complex with protein kinase C gamma (PKCg) to form a PKCg/binding partner complex; determining the quantity of PKCg/binding partner complex formed; and assessing the potential for impairment of the neuropsychological or cognitive function from the quantity of PKCg/binding partner complex formed, the impairment of the neuropsychological or cognitive function being associated with hypoxia and not connected with an ischemic event or the restriction of blood flow to the central nervous system. 
     
     
         15 . The method of  claim 14 , further comprising comparing the amount of PKCg/binding partner complex formed with an amount of PKCg/binding partner complex formed with a control sample, wherein said control sample is indicative of a known impairment of a neuropsychological or cognitive function of the central nervous system. 
     
     
         16 . The method of  claim 14 , further comprising monitoring the amount of PKCg/binding partner complex formed over a period of time. 
     
     
         17 . A method for diagnosing a disorder of a neuropsychological or cognitive function of the central nervous system of a patient comprising: contacting a sample obtained from said patient with a binding partner capable of forming a binding complex with PKCg to form a PKCg/PKCg binding partner complex, wherein detection of a PKCg/PKCg binding partner complex is diagnostic of said disorder, the disorder being associated with hypoxia and not connected with an ischemic event or the restriction of blood flow to the central nervous system. 
     
     
         18 . A kit for diagnosis of a disorder of the neuropsychological or cognitive function of the central nervous system of a patient comprising: a first substrate having immobilized thereon an anti-PKCg antibody or antibody fragment for contact with a sample obtained from the patient; a detectable label that is capable of binding to a PKCg/PKCg antibody complex; a second substrate which has bound thereto a PKCg/binding partner complex which is detectably labeled at a detection level that is representative of a disorder of a neuropsychological or cognitive function of the central nervous system of a similar patient, the disorder being associated with hypoxia and not connected with an ischemic event or the restriction of blood flow to the central nervous system. 
     
     
         19 . The kit of  claim 18 , further comprising a second anti-PKCg antibody reactive with another epitope of PKCg. 
     
     
         20 . The kit of  claim 18 , wherein said first antibody is immobilized on a solid support. 
     
     
         21 . The kit of  claim 20 , wherein the solid support is selected from the group consisting of a plastic multiwall plate, plastic or glass beads or rods, and a plastic or glass film. 
     
     
         22 . The kit of  claim 18 , wherein the antibody or antibody fragment is labeled. 
     
     
         23 . The kit of  claim 18 , further comprising one or more additional substrates each of which has bound thereto a PKCg/binding partner complex which is detectably labeled at a detection level that is representative of another disorder of a neuropsychological or cognitive function of the central nervous system of a similar patient. 
     
     
         24 - 26 . (canceled) 
     
     
         27 . The method of  claim 14 , wherein the patient's blood has a PaO 2  of between about 25 mm Hg and 80 mm Hg. 
     
     
         28 . The method of  claim 27 , wherein the hypoxia is associated with a condition selected from the group consisting of: altitude sickness HAPE, HACE, retinal encephalopathy, and hypoxic encephalopathy. 
     
     
         29 . The method of  claim 27 , wherein the hypoxia is associated with one selected from the group consisting of: a breathing disorder, apnea, a pulmonary disorder, a surgical procedure, administration of medication, a change in altitude and a change in barometric pressure. 
     
     
         30 . The method of  claim 17 , wherein the patient's blood has a PaO 2  of between about 25 mm Hg and 80 mm Hg. 
     
     
         31 . The method of  claim 30 , wherein the hypoxia is associated with a condition selected from the group consisting of: altitude sickness, HAPE, HACE, retinal encephalopathy, and hypoxic encephalopathy. 
     
     
         32 . The method of  claim 30 , wherein the hypoxia is associated with one selected from the group consisting of: a breathing disorder, apnea, a pulmonary disorder, a surgical procedure, administration of medication, a change in altitude and a change in barometric pressure.