Hello!
You need to be a little more specific: what are you planning on seeing: motor and/or cognitive improvement or you need a more molecular approach: number of new neurons if you are interested in them, etc!
Stroke is a complex pathology in humans and has a lot of aspects that are partially found in animal models or non at all! There are methods of testing motor and cognitive outcomes, even post-stroke depression. So it really a trail and error process. It also depends on the stroke model, a lot!!!
If you feel I can me of more help please let me know!
All the best in you experiments,
Bogdan
Depends. In humans anyway, the putative major antioxidant neuroprotectant is uric acid, which runs about 200-400 mcm. Animal models have only a fraction of this. Urate is about as good an antioxidant as ascorbate, etc. So this seems a reasonable target.
However, after early promising reports urate infusion in humans seems to have failed in stroke treatment. Links below. Alternate methods for raising urate are still in trials for Parkinsons. .
Similarly, in Astrazenica's antistroke "Saint" trials, the target level for NXY-059 (not quite as good an antioxidant as urate) was 127 mcm. However, this trial also failed.
Unfortunately, animal trials (for neuroprotection or whatever) with antioxidants do not transfer well to humans. This may be because in humans all that urate doesn't leave a lot of room for ectopic antioxidants to work. This includes urate itself.
What do work in human diseases are SODs and SOD-mimetics, tho these have not been tried for stroke per se.
http://newsroom.heart.org/news/adding-uric-acid-to-standard-stroke-clot-busters-reduces-stroke-disability
http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(14)70054-7/abstract
I welcome you, Kathiravan Kaliappan! (Sorry, I don’t know where is your first name) I completely agree with Bogdan. Efficiency of a preparation should be estimated on change of indicators which interest you. Since doses which are uneffective (if there are no literary data, it should be find such doses) and then, consistently increasing concentration of a dose at 5-10 times, to estimate dose-dependent positive effects and their range, and also to reveal possible negative effects, including the negative side effects. About rats. The adult rat has age beginning of two months and weight more than 200-220 grammes. Good luck and - Happy New Year and Christmas!
I assume this is a PK/PD question ?
Effective dose depends on compound and pharmacological target. Also you need to understand the pharmacodynamic relationship between target occupancy and effect. For some targets you only need relatively small (¨30%) target occupancy in order to see an effect, whereas for other targets you will need rather high occupancy (>90 %).
If we assume you need 95% target occupancy you can use Ki (Assuming we are talking about an antagonist) to estimate the effective dose. Typically you could use a dose of 2 or 3 times Ki to be sure to get that level of target occupancy. That ofcourse only works in an i.v. injection setting. You would have to know a bit more about the distributon properties of the compound in order to calculate a more exact dose.
The question posted is How to calculate the effective dose of a particular compound in rats?
By definition, an effective dose is the dose of the compound or agent at the target organ that has an effect at the target organ. By your question, I presume that you do not have a means of measuring the dose of the agent or compound at the target organ that produces the effect of interest and therefore, you are looking to "calculate" the dose at the target organ.
Where appropriate pharmaco-kinetic models exist for your specific rat species, you might use them to calculate the dose at the target organ. Such models presume that you can model the distribution and fate a compound or agent under certain conditions within the rat, but often fail to account for specific protein binding, selective or active transport, and other processes that might be specific for the compound or agent of interest.
In toxicology, scientists have devised several means of estimating the "effective dose" at the target organ from various dosing protocols (e.g., oral gavage, consumption of food or water, percutaneous injection, dermal absorption, etc.). Such estimates, while useful, often rely on assumptions that may or may not hold true for your species of rat (e.g., body weight, pharmaco-kinetic differences, etc.). Roughly, toxicologists are generally interested in the concentration of the compound or agent in blood over time, with the area under the curve (concentration v time) describing the estimated dose to the target organ.
To appropriately answer your question, I would need to know the compound or agent administered, the species of rat, the target organ and effect of interest.
In humans, we see dosage for anesthesia vary by a factor from 1/7 to 7X, for a total spread of a factor of ~50. (There is a saying among dentists that 'redheads' never seem to get enough anesthestic, as they always complain.) In epilepsy patients in the hospital for brain resection, we have done in-vitro tests of their blood brain barrier (Flocel.com). We have seen the transmission rate of the drug through the BBB can be one-tenth of "normals".
What can cause this large difference of dosage include a number of factors in addition to the ones listed above. For the BBB, we see that the endothelial cells in the capilaries vary from person to person depending on their genome. The drug transmission rate through the cell membrane varies. Going across the cell, the drug can be metabolized. Then the transmission rate through the outgoing membrane of the metabolite will also vary based on the genome. The same effects are seen in the stomach, liver, etc for oral applications of drugs. All adding to dosage variation.
The bottom line, it is all trial and error as the efficacy can vary by a factor as much as 100 due to genome variations. So, depending on the variety in the genome of your rat species, you may have additional trials.