Premium
P2‐006: BIOCHEMICAL ANALYSIS OF ABETA TOXIC CONFORMER IN HUMAN AUTOPSIED BRAINS AND CEREBROSPINAL FLUID
Author(s) -
Tomidokoro Yasushi,
Ishii Kazuhiro,
Tamaoka Akira
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.05.679
Subject(s) - conformational isomerism , cerebrospinal fluid , epitope , monoclonal antibody , western blot , chemistry , pathology , oxidative stress , medicine , biochemistry , antibody , molecule , immunology , gene , organic chemistry
kit (Pierce) as per manufacturer’s instructions. The serum samples and the samples from different brain regions including olfactory lobes (OL), cortex (CTX), hippocampus (HP), and cerebellum (CBM) were collected at different time-points (30 min, 2h, 8h, 12h, 24h) following a single bolus IN and IPadministration. The brain regions were homogenized in sterile saline (mg brain tissue/ml sterile saline) and 100ml of homogenate equating 100mg of brain tissue and 100ml of serum samples was read in the gamma counter (RRC Common Resource-UIC). The data were expressed as cpm/100mg. Results: Results show that the brain uptake of IN delivered therapeutics was w4-5 times greater than that after IP delivery. Although the entry of test therapeutics in different brain regions was observed to be spaced out according to the distance of brain region from the site of administration, the peak resident time of all test therapeutics for all brain regions was retained between 4-8h both after IN administration. Currently observed fading of radioactive counts beyond 12h post IN administration and further decrease incounts to the base levels by 24h post IN administration, was consistent with the known mouse brain ventricular bulk-flow of 24h. Approximately, 1/5 th of the total IN dose was found to enter the blood. IP delivered test therapeutics exhibited much higher serum values than the brain uptake values at all experimental time points.Conclusions: Intranasal administration is an effective means of delivering therapeutics to the brain.