ABSTRACT
Lesion studies have suggested that the auditory cortex may not be involved in many aspects of hearing. A recent report casts doubt on this long-held view by showing that reversible inactivation of the auditory cortex leads to a transient impairment in tone detection and frequency discrimination.
Subject(s)
Auditory Cortex/physiology , Hearing/physiology , Animals , HumansABSTRACT
We evaluated the delivery of 14C-cytosine arabinoside (AraC) to rat brain by: 1) intravenous (IV) bolus, by 2) intrathecal (IT) and 3) intraventricular (IVT) infusion, and by 4) convection-enhanced delivery (CED) into the caudate nucleus. Plasma and brain AraC metabolites were measured with HPLC, and distribution and concentration of 14C-AraC in brain sections were measured by quantitative autoradiography. After IV administration, the alpha and beta plasma half-lives were 1.9 and 46.5 min, respectively. The blood-to-brain transfer constant of AraC was 2.5+/-1.4 microliter g(-1) min(-1), compatible with high water solubility. After IT and IVT administration, tissue levels were high at the brain and ventricular surfaces, but declined exponentially into brain. After CED, maximum brain levels were up to 10,000 times higher than the IV group, and the distribution pattern was one of high 14C-AraC concentration in the convective component, with exponentially declining concentrations outside this region. The rate loss constant from brain was 0.002+/-0.0004 min(-1), suggesting that AraC was accumulating in brain cells. AraC was metabolized into uracil arabinoside within the brain. 14C-AraC was infused into 1 dog and distributed widely in the ipsilateral hemisphere. These studies suggest that delivery of AraC to brain parenchyma by the IV, IT or IVT routes will be subtherapeutic. Delivery by CED can achieve, and maintain, therapeutic levels of AraC in the brain, and should be further evaluated as a potential method of drug delivery.
Subject(s)
Brain/metabolism , Caudate Nucleus/metabolism , Cytarabine/administration & dosage , Cytarabine/pharmacokinetics , Animals , Carbon Radioisotopes , Cytarabine/blood , Dogs , Half-Life , Infusions, Parenteral , Injections, Intravenous , Injections, Intraventricular , Injections, Spinal , Rats , Rats, Sprague-Dawley , Tissue DistributionABSTRACT
It has become important for clinicians to increase their understanding of the breadth, mechanism, and neurosurgical implications of viral illnesses of the central nervous system. These needs can now be more safely and accurately addressed using stereotactic neurosurgical techniques. This article provides an introduction to these disease and identifies the neurosurgical issues that may be raised in their diagnosis and treatment.
