Intracranial distribution

Mannitol Physical osmotic effect on tissue water distribution because it is retained in the vascular compartment Marked increase in urine flow, reduced brain volume, decreased intraocular pressure, initial hyponatremia, then hypernatremia Renal failure due to increased solute load (rhabdomyolysis, chemotherapy), increased intracranial pressure, glaucoma IV administration Toxicity Nausea, vomiting, headache... 

Less invasive methods of delivering nonviral vectors to the CNS would be more desirable. Despite the minimal inflammatory profile of intracranial delivery of DNA-lipid complexes, the potential exists for surgery-induced adverse events, while the relatively limited volume of distribution obtained from stereotactic infusion makes the approach rather infeasible when attempting to treat diseases that involve expansive regions of the brain. To that end, methodologies have been developed to enable the injection of modified... 

Cunningham J, Oiwa Y, Nagy D, Podsakoff G, Colosi P, Bankiewicz KS (2000) Distribution of AAV-TK following intracranial convection-enhanced delivery into rats. Cell Transplant 9 585-594. 

Saltzman WM, Mak MW, Mahoney MJ, Duenas ET, Cleland JL. Intracranial delivery of recombinant nerve growth factor release kinetics and protein distribution for three delivery systems. Pharm Res 1999 16 232-240. 

BBB disruption and development of vasogenic edema. Decreased perfnsion pressnre and decreased cerebral blood flow lead to the failnre of the Na /KVATPase pump, which then leads to cytotoxic edema [74]. Parenchymal hndings on MR include cerebral swelling, venons infarctions, and gross or petechial intracranial hemorrhage, often in a nonarterial distribution. 

Neuropathology and neuroimaging cannot be distinguished among children with hypothyroid diseases. Specific distributions of intracranial calcifications are common in hypothyroid diseases. 

A second experiment employed the same rat intracranial model to compare BCNU release kinetics and biodistribution using pCPP SA (20 80) copolymer delivery vs. direct stereotactic injection (85). Following implantation or injection, tritiated BCNU allowed drug distribution assessment by... 

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