clinical trials have shown that ric after subarachnoid hemorrhage is feasible, safe, and well tolerated, and can prevent delayed neurological deficits. traumatic brain injury traumatic brain injury (tbi) shares many pathophysiological pathways with acute stroke, and ischemic preconditioning increases the brain's resistance to injury. animal models of stroke (both open-skull and closed-skull models) show that ric improves cerebral blood flow; reduces ischemic injury, edema, and cell death; and improves functional outcomes. a small randomized clinical trial in severe tbi also showed that patients who received ric had lower levels of brain injury biomarkers. vascular cognitive impairment reduced cerebral blood flow is an early finding in vascular cognitive impairment (vci). cardiovascular risk factor control is currently the only management option for vci, but observational studies suggest that exercise slows down cognitive decline. in a mouse model that reproduced the damage seen in patients with vci (white matter damage, cerebral hypoperfusion, inflammation, blood–brain barrier damage, and cognitive deficits), daily ric for two weeks increased cerebral blood flow, and this increase persisted for one week after cessation of conditioning. moreover, mice that underwent ric had less inflammation, less white and gray matter damage, less β‑amyloid deposition, and improved cognition. timing and protocol the ric stimulus can be applied to different tissues in the body. either the upper limb (arm) or the lower limb (leg) may be used; however, because it is easier and more comfortable, most clinical trials use the upper limb. researchers investigating the optimal dosing for the ric stimulus have concluded that the upper limb is superior to the lower limb, that ric on one limb generates an equivalent response to ric on two limbs, and that maximal benefit occurs at 4–6 cycles. timing the non-invasiveness and ease of application of ric have allowed it to be studied in more situations than the original, invasive ischemic preconditioning, which was only realistically applicable in elective surgery. studies have examined the effects of ric applied at different times: pre-conditioning: ric is applied within the hour prior to an intervention (e.g., elective cardiothoracic and surgical procedures) per-conditioning: ric is applied at the time of the ischemic event (e.g., evolving heart attack, acute stroke, or trauma) chronic conditioning: ric is applied daily for a period of time after an ischemic event (e.g., after a heart attack or stroke, or in chronic conditions such as peripheral vascular disease or ulcerative colitis) the term "post-conditioning" is used to describe short, intermittent inflations of an intra-coronary balloon at the time of reperfusion, and does not refer to ric on a limb. delayed post-conditioning is synonymous with chronic conditioning. manual vs. automated conditioning remote ischemic conditioning on the limb is mostly done by healthcare professionals, using a manual blood-pressure cuff and a stopwatch. the standard ric protocol, used in the majority of clinical trials, consists of four cycles of five minutes of inflation at 200mmhg, followed by five minutes of deflation. this is the original conditioning protocol described by murry et al. based on examinations of energetic depletion of the cell. automated conditioning one automated device is approved in europe and canada for the delivery of remote ischemic conditioning: the autoric device, which delivers four cycles of five minutes of inflation at 200mm hg followed by five minutes of deflation to the upper limb. in a comparative study of this device and manual conditioning, the autoric device was shown to be much easier to use.