Delayed inhibition of angiotensin II receptor type 1 reduces secondary brain damage and improves functional recovery after experimental brain trauma*

Abstract

The results indicate that angiotensin II receptor type 1 plays a key role in the development of secondary brain damage after brain trauma. Inhibition of angiotensin II receptor type 1 with a delay of up to 4 hrs after traumatic brain injury effectively reduces lesion volume. This reduction makes angiotensin II receptor type 1 a promising therapeutic target for reducing cerebral inflammation and limiting secondary brain damage.

Candesartan, an Angiotensin II AT1-Receptor Blocker and PPAR-γ Agonist, Reduces Lesion Volume and Improves Motor and Memory Function After Traumatic Brain Injury in Mice

“…We therefore investigated the effect of administering candesartan to mice just before they received a controlled cortical impact (CCI) injury to determine whether short-or long-term inhibition of central AT 1 Rs would reduce the cortical and hippocampal damage and hence protect against cognitive impairment. While we were completing these data, a report was published demonstrating that administration of low doses of candesartan to mice within 4 h of TBI prevented secondary brain damage and reduced cerebral inflammation at 24 h post-injury (Timaru-Kast et al, 2012). Our studies confirm and extend these observations.…”

“…Indeed, beneficial effects of candesartan after stroke have been shown for doses that are not hypotensive (Omura-Matsuoka et al, 2009). The results of Timaru-Kast et al (2012), show that post-injury administration of candesartan up to 4 h after injury are beneficial to recovery when assessed at 24 h after injury. We have shown that the beneficial cognitive effects of candesartan can be detected up to 28 days after injury.…”

“…Injection of 1 mg/kg candesartan immediately following injury may be more detrimental than injecting it 5 h before injury. Indeed, Timaru-Kast et al, (2012) found that 1 mg/kg significantly lowered blood pressure. With the use of indirect tail cuff measurements, we found only a slight nonsignificant drop in blood pressure (Figure 3).…”

The antioxidative, non-psychoactive tricyclic phenothiazine reduces brain damage after experimental traumatic brain injury in mice

“…This test has been established for mouse TBI and evaluates motor function, alertness, balancing, and general behavior [17].…”

Disorders of carbohydrate metabolism in experimental brain injury

“…The hypermetabolic syndrome develops in different extremal states and in patients with cerebral trauma also [11]. Secretion of catecholamines, glucocorticoids and angiotensin is stimulated by trauma and stress [12]. Oxygen necessity of brain increase, but disorders of circulation, accumulation of lactate, formation of acidosis lead to hypoxia [13].…”