Can clinical therapy change brain metabolism?

	Population	N	Methods	Findings
Vespa et al., 2006	TBI	47	Nonrandomized consecutive design comparing brain chemistry in patients managed with “loose” versus “intensive” insulin therapy	Patients in the intensive therapy group had lower brain glucose concentrations associated with an increase in glutamate and L/P ratio
Oddo et al., 2008	SAH, TBI, ICH, Ischemic stroke	20	Multivariate logistic regression used to examine relationship between multiple physiologic and microdialysis variables and in-hospital mortality	Systemic glucose concentration and insulin dose were independent predictors of metabolic crisis and mortality
Helbok et al., 2010	SAH	28	Multivariate logistic regression to examine relationship between serum glucose and microdialysis patterns	Reductions in serum glucose by 25 % were associated with episodes of elevated L/P ratio and decreased glucose
Vespa et al., 2012	TBI	13	Prospective within subject crossover trial of “tight” versus “loose” glycemic control and measured glucose metabolism using FDG PET	“Tight” glycemic control was associated with elevated L/P ratio and decreased brain glucose as well as an increase in brain global glucose uptake
Tolias et al., 2004	TBI	52	Prospective study of 24 h of normobaric hyperoxia. Microdialysis compared with baseline and also with age, GCS, and ICP matched controls	Normobaric hyperoxia treatment was associated with an increase in brain glucose and a decrease in L/P ratio as well as a reduction in ICP
Nortje et al., 2008	TBI	11	Brain tissue oxygen, cerebral microdialysis, and 15OPET scans were performed at normoxia and hyperoxia	Normobaric oxygen was associated with an increase in brain tissue oxygen; however, the association with microdialysis changes and oxygen metabolism on PET was variable
Rockswold et al., 2010	TBI	69	Patients randomized to normobaric O2 treatment, hyperbaric O2 treatment or control. Brain oxygen, microdialysis and ICP were monitored	Both normobaric and hyperbaric hyperoxia improved microdialysis parameters. Hyperbaric O2 had a more robust and long lasting effect
Marion et al., 2002	TBI	20	30 min of hyperventilation performed at two time points (24 h and 3 days) after injury, microdialysis and local cerebral blood flow in vulnerable tissue was studied	Brief hyperventilation was associated with increased glutamate and elevated lactate and L/P ratio. This relationship was more marked at the early time point
Hutchinson et al., 2002	TBI	13	Hyperventilation with simultaneous PET scan to measure oxygen extraction fraction (OEF)	Hyperventilation was associated with a reduction in microdialysis glucose and an elevated OEF
Sakowitz et al., 2007	TBI	6	ICP, brain oxygen, and microdialysis parameters were recorded before and after therapeutic doses of mannitol	Microdialysis concentrations rose up to 40 % over the first hour after mannitol in a nonspecific pattern
Helbok et al., 2011	SAH ICH	12	ICP, brain oxygen and microdialysis parameters were measured before and after therapeutic mannitol doses	Mannitol therapy was associated with a decrease in ICP as well as an 18 % decrease in L/P ratio without a change in brain glucose
Ho et al., 2008	TBI	16	ICP, brain oxygen, autoregulation, and microdialysis parameters were measured before and after decompressive craniectomy for refractory intracranial hypertension. Outcome was measured with 6 month GOS	There was a decrease in microdialysis lactate, L/P ratio and glycerol in patient treated with decompressive craniectomy in those who had a favorable outcome
Nagel et al., 2009	SAH	7	Data from a database was retrospectively studied to determine the effect of decompressive craniectomy on cerebral metabolism. 12 month GOS assessed for outcome	In patients treated with decompressive craniectomy glucose and glycerol were lower after the procedure. However, L/P ratio and glutamate did not change
Soukup et al., 2002	TBI	58	ICP, brain oxygen, and microdialysis parameters were measured before and after mild therapeutic hypothermia was used to treat refractory ICP	Therapeutic hypothermia was associated with lower microdialysis glucose and lactate consistent with decreased metabolic demand
Berger et al., 2002	CVA	12	ICP and microdialysis parameters measured before and during therapeutic hypothermia used as rescue therapy for large MCA infarcts	Glutamate, lactate and pyruvate were all affected by therapeutic hypothermia. However, the degree of change varied depending on the probe position