Ontogeny of Adenosine Production and Degradation and ItsImplications in Neonatal Cerebral Blood Flow Regulation
Bibliographic record
Abstract
Adenosine is a neuromodulator and potent vasoactive metabolite involved in various CNS regulatory mechanisms. We have recently shown that the newborn has maturationally related deficiency in adenosine production. The brains of Sprague-Dawley rats studied at ages 1, 7, 21 and 60 days (n = 6-12/group) showed that adenosine and its metabolites (measured by high-pressure liquid chromatography) is deficient in the newborn. Adenosine brain concentration was 0.99 nmol/g brain in newborn rats (day 0-1) and progressively increased postnatally to an adult value of 14.4 nmol/g brain. Inosine, a degradative product of adenosine by deaminase is significantly increased in newborns (mean ± SEM = 48.3 ± 14.3 nmol/g brain) relative to the 7-day-old rat (7.4 ± 1.1 nmol/g brain) and to the adult (17.8 ± 3.6 nmol/g brain). Thus, newborns have deficient adenosine brain concentration and this is due in part to increased deamination of adenosine. However, adenosine brain production may be augmented by ischemic-hypoxic insult. This was tested in 2 age groups of rats; 7 days old (n = 35) and adults (n = 35). Under nembutal anesthesia, bilateral carotid arteries were exposed and loosely tied, then both carotids were ligated and 5 animals from each group were decapitated and heads immediately frozen in liquid N(2) at 5, 15, 30, 60, 120 and 300 s after ligation. Similar animals with carotids exposed but not ligated served as control (time zero). Brains were removed and assayed for adenosine and metabolites using high-pressure liquid chromatography. Adenosine brain concentration in the 7-day-old rat increased from 15.85 ± 6.33 to 43.66 ±5.19 nmol/g brain within 5 s after bilateral carotid artery ligation. Similarly, in the adult rats, adenosine brain concentration increased from 13.26 ± 1.03 to 40.52 ± 15.02 nmol/g brain 5 s after carotid ligation. Thus, basal brain adenosine levels are similar in both groups studied with brisk and immediate response in adenosine production following carotid ligation indicating that adenosine response to ischemic- hypoxic insult is intact in newborns. Adenosine administered via the carotid artery at doses of 10^-6 to 10^-3 had no effect on cerebral blood flow in the newborn piglet. However, the drug, when given via a ventriculocisterna magna perfusion technique increased regional blood flow to those areas exposed to the drug. Further studies are needed to define the role of adenosine in neonatal CBF autoregulation and its possible significance in perinatal brain damage.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".