Sex-Specific Effects of Progesterone on Early Outcome of Intracerebral Hemorrhage.

BACKGROUND: Preclinical evidence suggests that progesterone improves recovery after intracerebral hemorrhage (ICH); however, gonadal hormones have sex-specific effects. Therefore, an experimental model of ICH was used to assess recovery after progesterone administration in male and female rats. METHODS: ICH was induced in male and female Wistar rats via stereotactic intrastriatal injection of clostridial collagenase (0.5 U). Animals were randomized to receive vehicle or 8 mg/kg progesterone intraperitoneally at 2 h, then subcutaneously at 5, 24, 48, and 72 h after injury. Outcomes included relevant physiology during the first 3 h, hemorrhage and edema evolution over the first 24 h, proinflammatory transcription factor and cytokine regulation at 24 h, rotarod latency and neuroseverity score over the first 7 days, and microglial activation/macrophage recruitment at 7 days after injury. RESULTS: Rotarod latency (p = 0.001) and neuroseverity score (p = 0.01) were improved in progesterone-treated males, but worsened in progesterone-treated females (p = 0.028 and p = 0.008, respectively). Progesterone decreased cerebral edema (p = 0.04), microglial activation/macrophage recruitment (p < 0.001), and proinflammatory transcription factor phosphorylated nuclear factor-x03BA;B p65 expression (p = 0.0038) in males but not females, independent of tumor necrosis factor-α, interleukin-6, and toll-like receptor-4 expression. Cerebral perfusion was increased in progesterone-treated males at 4 h (p = 0.043) but not 24 h after injury. Hemorrhage volume, arterial blood gases, glucose, and systolic blood pressure were not affected. CONCLUSIONS: Progesterone administration improved early neurobehavioral recovery and decreased secondary neuroinflammation after ICH in male rats. Paradoxically, progesterone worsened neurobehavioral recovery and did not modify neuroinflammation in female rats. Future work should isolate mechanisms of sex-specific progesterone effects after ICH.

Delay of stroke onset by milk proteins in stroke-prone spontaneously hypertensive rats.

BACKGROUND AND PURPOSE: There is an inverse association between dairy food consumption and the incidence of stroke in observational studies. However, it is unknown whether the relationship is causal or, if so, what components in milk are responsible for reducing the incidence of stroke. METHODS: Stroke-prone spontaneously hypertensive rats were fed diets comprising amino acids, proteins from different sources (casein, whey, soybean, or egg white), or fats from different sources (butter, beef tallow, or cocoa butter) and the onset of stroke and lifespan were examined. RESULTS: Increasing the amount of dietary casein (5% to 55% of caloric intake) markedly delayed the onset of stroke. However, when stroke-prone spontaneously hypertensive rats were fed diets containing 55% of caloric intake as protein, rats fed casein or whey protein, a major component of milk, displayed a delayed onset of stroke compared with rats fed soybean or egg white protein. Rats fed an amino acids diet containing the same amino acids composition as casein did not have a delay in the onset of stroke. Increasing dietary fats, including butter as well as beef tallow and cocoa butter, did not affect the onset of stroke. All diets did not affect blood pressure in the early stage. CONCLUSIONS: These data suggest that the inverse association between dairy food consumption and incidence of stroke in epidemiological studies is causal and that peptides in milk protein, but not fat, might be responsible for this effect.

Dietary supplementation of omega-3 polyunsaturated fatty acids worsens forelimb motor function after intracerebral hemorrhage in rats.

Dietary intake of omega-3 polyunsaturated fatty acids has been associated with decreased clotting ability and increased risk of hemorrhagic stroke. The aim of the current study was to assess the effect of dietary supplementation of omega-3 polyunsaturated fatty acid on functional outcome after hemorrhagic stroke. Rats were maintained on a diet containing approximately 30% of energy as either fish oil (rich in omega-3 fatty acids) or safflower oil (rich in omega-6 fatty acids) and subjected to either intracerebral hemorrhage or sham surgery. Behavioral tests, infarct measurement, and MR imaging techniques were used to assess outcome. While there was no significant difference in infarct volume between rats on different diets, animals maintained on a diet enriched with fish oil exhibited increased cerebral blood flow after surgery. These animals were significantly more impaired than rats fed the safflower-oil-enriched diet in tests of forelimb dexterity and fine motor control. These results suggest that high intake of omega-3 polyunsaturated fatty acids may not only increase the risk of hemorrhagic stroke as shown in previous studies, but most importantly may lead to a more severe motor impairment and a poorer functional outcome after such an event.

Cerebral hemorrhage associated with vitamin K deficiency in congenital tuberculosis treated with isoniazid and rifampin.

We report a male infant with congenital tuberculosis who developed cerebral hemorrhage associated with vitamin K deficiency during treatment with isoniazid and rifampin. Despite an absence of risk factors for vitamin K deficiency, the severe hemorrhagic disorder occurred at 4 months of age. We speculate that vitamin K deficiency in the present case may have resulted from a synergic effect of antituberculosis agents and immaturity of vitamin K metabolism and/or its absorption.