Therapeutic effects of bryostatins, bryologs, and other related substances on head trauma-induced memory impairment and brain injury

Abstract

The invention provides for the use of protein kinase activators or boosters of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) or other neurotrophic factors to treat head trauma. Specifically, the present invention provides methods of treating head trauma comprising the steps of identifying a subject having suffered a head trauma and administering to said subject an amount of a pharmaceutical composition comprising a protein kinase C (PKC) activator or 4-methylcatechol acetic acid (MCBA) and a pharmaceutically acceptable carrier effective to treat at least one symptom of head trauma.

1 - 19 . (canceled) 
     
     
         20 . A method of treating post-head trauma memory deficits resulting from brain injury comprising the steps of identifying a human subject having suffered a brain injury resulting from head trauma and administering to said subject an amount of a pharmaceutical composition comprising a protein kinase C (PKC) activator, and a pharmaceutically acceptable carrier effective to treat at least one symptom of head trauma, wherein the PKC activator is bryostatin-1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 or neristatin-1, and
 wherein the administration is initiated within 3 days of the head trauma and is continued for a duration in a range from about 1 week to about 12 weeks.   
     
     
         21 . A method of treating post-head trauma memory deficits resulting from brain injury comprising the steps of identifying a human subject having suffered a brain injury resulting from head trauma and administering to said subject an amount of a pharmaceutical composition comprising a protein kinase C (PKC) activator, and a pharmaceutically acceptable carrier effective to treat at least one symptom of head trauma, wherein the PKC activator is bryostatin-1, and
 wherein the administration is initiated within 3 days of the head trauma and is continued for a duration in a range from about 1 week to about 12 weeks.   
     
     
         22 . A method of treating post-head trauma memory deficits resulting from brain injury comprising the steps of identifying a human subject having suffered a brain injury resulting from head trauma and administering to said subject an amount of a pharmaceutical composition comprising a protein kinase C (PKC) activator, and a pharmaceutically acceptable carrier effective to treat at least one symptom of head trauma, wherein the PKC activator is bryostatin-2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18, and
 wherein the administration is initiated within 3 days of the head trauma and is continued for a duration in a range from about 1 week to about 12 weeks.   
     
     
         23 . The method of  claim 20 , wherein the PKC activator is neristatin-1. 
     
     
         24 . The method of  claim 20 , wherein the PKC activator has a molecular weight from about 600 to 755 and an affinity for PKC from about 0.25 nM to 10 μM. 
     
     
         25 . The method of  claim 20 , wherein said administration is initiated within 1 day of said head trauma. 
     
     
         26 . The method of  claim 20 , wherein said administration is initiated within 2 days of said head trauma or 3 days of head trauma. 
     
     
         27 . The method of  claim 20 , wherein said administration is initiated between 1 and 2 days of said head trauma. 
     
     
         28 . The method of  claim 20 , wherein said administration is initiated between 1 and 3 days of said head trauma. 
     
     
         29 . The method of  claim 20 , wherein the treatment is continued for a duration of 1 week. 
     
     
         30 . The method of  claim 20 , wherein the treatment is continued for a duration of 2 weeks, 3 weeks, or 4 weeks. 
     
     
         31 . The method of  claim 20 , wherein the treatment is continued for a duration of 6 weeks. 
     
     
         32 . The method of  claim 21 , wherein said administration is initiated within 1, 2, or 3 days of said head trauma. 
     
     
         33 . The method of  claim 22 , wherein said administration is initiated within 1, 2, or 3 days of said head trauma. 
     
     
         34 . The method of  claim 23 , wherein said administration is initiated within 1, 2, or 3 days of said head trauma. 
     
     
         35 . The method of  claim 21 , wherein said administration is initiated between 1 and 3 days of said head trauma. 
     
     
         36 . The method of  claim 22 , wherein said administration is initiated between 1 and 3 days of said head trauma. 
     
     
         37 . The method of  claim 21 , wherein the treatment is continued for a duration of 1 week, 2 weeks, 3 weeks, 4 weeks, or 6 weeks. 
     
     
         38 . The method of  claim 22 , wherein the treatment is continued for a duration of 1 week, 2 weeks, 3 weeks, 4 weeks, or 6 weeks. 
     
     
         39 . The method of  claim 23 , wherein the treatment is continued for a duration of 1 week, 2 weeks, 3 weeks, 4 weeks, or 6 weeks.