Neurosurgical procedures, carried out routinely in health institutions, present postoperative complications that result from unavoidable brain injury inflicted by surgical maneuvers. These maneuvers, which include incisions, electrocauterization, and retraction, place brain tissue at the margins of the operative site at risk of injury. Brain edema is a major complication that develops subsequent to this surgically induced brain injury. In the present review, we will discuss type of injury as well as the animal model available to study it. In addition, we will discuss potential mediators, including vascular endothelial growth factor, metalloproteinases, and cyclooxygenases, which have been tested in in vivo experimental studies and have been shown to be potential targets for the development of clinical therapies for neuroprotection against brain edema.