ABSTRACT Millions of people worldwide suffer annually from severe traumatic brain injury, stroke, status epilepticus and anoxia after cardiac arrest. These brain insults lead to high mortality, morbidity and disability unless rapidly and properly treated. Rapid cooling can significantly mitigate brain injuries by notably reducing swelling, inflammation, metabolism, and oxygen consumption ultimately preserving neurological function and enhancing recovery. Unfortunately, current hypothermic intervention requires prolonged systemic body cooling and suboptimal rewarming. This limitation results in healthy organ dysfunction and diminishes the benefits of reduced brain temperature. Selective brain cooling through external head refrigeration shows some promises, but cooling is limited to the brain surface. Other proposed selective brain cooling methods rely on inconvenient, expensive, and potentially dangerous fluid circulation systems. Therefore, an effective, safe, convenient, and affordable device to rapidly cool the injured brain without affecting negatively other organs remains an unmet crucial clinical need. To address this urgent need, we conceived a novel rapid cooling device for intracranial use or as a stylet for widely used external ventricular drain (EVD) catheters. EVD catheters are used globally to monitor and reduce intracranial pressure (ICP) in injured patients through cerebrospinal fluid (CSF) removal. Since CSF circulates throughout the entire central nervous system, EVD catheters are an ideal conduit for brain and spinal cord cooling. BREEZE (Brain Rapid Enthalpy Extractor with Zero-liquid Exchange) would conveniently replace current stylets guiding EVD catheters into ventricles. Without interfering with CSF drainage, BREEZE could induce rapid brain cooling a novel heat pipe- and ionic wind-based design. By exploiting capillary action and vapor expansion, the heat-pipe transfers rapidly brain heat to an ionic wind fan, which dissipates it to colder external environments. Our long-term objective is to improve neurological outcome of brain-injured patients by translating our low-cost groundbreaking cooling technology into clinical practice. The rationale for our approach is that by integrating heat-pipe, thermoelectric cooling, ionic wind, and adaptive control, we can provide effective selective cerebral cooling to mitigate acute brain injury and improve patient recovery. Our underlying hypotheses are that our cutting-edge cooling technology can be miniaturized into an EVD-compatible stylet (H1), adaptively controlled to a user-defined thermal profile in biomimetic phantom (H2) and in non-human primates (H3). Thus, we propose these specific aims: (SA1) Optimize BREEZE technology into a 1.5mm dia brain cooling intracranial/ventricular stylet; (SA2) Build an adaptive brain-cooling algorithm for BREEZE using a bio-accurate model/phantom; (SA3) Study initial feasibility of BREEZE selective/adaptive brain cooling in five non-human primates....