Introduction: We previously showed that the decrease in critical cerebral perfusion pressure (CPP) to 30 mmHg obtained by cerebral blood flow (CBF) autoregulation curve with increasing intracranial pressure (ICP), compared to 60 mmHg when CPP is reduced by decreasing arterial pressure, was due to pathological microvascular shunting at high ICP. We concluded that determination of the critical CPP by the CBF autoregulation curve is not applicable to brains at high ICP. We hypothesized that dynamic ICP (PRx) and cerebrovascular (CVRx) reactivity would better detect impaired autoregulation. Methods: In vivo 2-photon laser scanning microscopy (2PLSM) over the rat parietal cortex was used to measure microvascular (MV) flow velocity, NADH fluorescence (hypoxia) and blood brain barrier (BBB) integrity (fluorescein dye extravasation). Doppler flow, temperatures, ICP, arterial pressure and blood gases were monitored. CPP was reduced stepwise from 70 to 50 and 30 mmHg by increasing ICP. At each CPP, a transient 10 mmHg rise in mean arterial pressure (MAP) was induced by i.v. dopamine bolus. PRx is a ratio of the ICP change in response to MAP increase (PRx=ΔICP/ΔMAP). CVRx is a ratio of the change in CBF with MAP change (CVRx=ΔCBF/ΔMAP). Results: CBF autoregulation curves indicated a critical CPP of 30 mmHg at high ICP. However, our 2PLSM data show that reduction of CPP to 50 mmHg by increasing ICP caused a transition from capillary to microvascular shunt flow associated with brain edema, hypoxia and BBB opening. At a normal CPP (70 mmHg) blood pressure challenge caused no change in ICP (PRx=-0.03±0.07, n=5), i.e., intact pressure reactivity. When CPP was decreased to 50 and 30 mmHg by ICP elevation, PRx increased to 0.09±0.16 and 0.26±0.14, respectively (n=7, p<0.05). Similarly at a normal CPP MAP challenge showed a CVRx of -0.02±0.05, reflecting intact cerebral autoregulation. When CPP was decreased to 50 and 30 mmHg by ICP, CVRx increased to 0.11±0.13 and 0.26±0.14, respectively, reflecting impaired autoregulation (p<0.05). Conclusions: As determined by PRx and CVRx at high ICP the critical CPP is 50 mmHg where MV shunting, brain edema, hypoxia and BBB leakage begin to occur which is higher than the 30 mmHg determined by static autoregulation.