The published guidelines point out the need for the development of methods that individualize patient cerebral perfusion management and minimize secondary ischemic complications associated with traumatic brain injury. A laboratory method has been developed to determine model-derived assessments of cerebrovascular resistance (mCVR) and cerebral blood flow (mCBF) from cerebrovascular pressure transmission, and the dynamic relationship between arterial blood pressure (ABP) and intracranial pressure (ICP). The aim of this two-fold study is to (1) evaluate relative changes in the model-derived parameters of mCVR and mCBF with the corresponding changes in the pial arteriolar vascular parameters of pial arteriolar resistance (PAR) and relative pial arteriolar blood flow (rPABF); and (2) examine the efficacy of the proposed modeling methodology for continuous assessment of the state of cerebrovascular regulation by evaluating relative changes in the model-derived parameters of CBF and cerebrovascular resistance in relation to changes of cerebral perfusion pressure prior to and following fluid percussion brain injury. Changes of ABP, ICP, PAR, relative arteriolar blood flow (rPABF) and the corresponding model-derived parameters of mCBF and mCVR induced by acute hypertensive challenge were evaluated before and following fluid percussion injury in piglets equipped with cranial windows. Before fluid percussion, hypertensive challenge resulted in a significant increase of PAR and mCVR, whereas both rPABF and mCBF remained constant. Following fluid percussion, hypertensive challenge resulted in a significant decrease of PAR and mCVR and consistent with impaired cerebrovascular regulation. Hypertensive challenge significantly increased both rPABF and mCBF, which approximately doubled with increased CPP with correlation values of r = 0.96 (P < 0.01) and r = 0.97 (P <or= 0.01), respectively. The assessment of model-derived cerebrovascular resistance and CBF with changes of CPP provides a means to monitor continuously the state of cerebrovascular regulation.