Applications of the Morris water maze in the study of learning and memory.

Summary The past decade has resulted in a rapid increase in knowledge of mechanisms underlying brain injury induced by intracerebral haemorrhage (ICH). Animal studies have suggested roles for clot-derived factors and the initial physical trauma and mass effect as a result of haemorrhage. The coagulation cascade (especially thrombin), haemoglobin breakdown products, and inflammation all play a part in ICH-induced injury and could provide new therapeutic targets. Human imaging has shown that many ICH continue to expand after the initial ictus. Rebleeding soon after the initial haemorrhage is common and forms the basis of a current clinical trial using factor VIIa to prevent rebleeding. However, questions about mechanisms of injuries remain. There are conflicting data on the role of ischaemia in ICH and there is uncertainty over the role of clot removal in ICH therapy. The next decade should bring further information about the underlying mechanisms of ICH-induced brain injury and new therapeutic interventions for this severe form of stroke. This review addresses our current understanding of the mechanisms underlying ICH-induced brain injury.

Mechanisms of brain injury after intracerebral haemorrhage

Empathizing is the capacity to predict and to respond to the behavior of agents (usually people) by inferring their mental states and responding to these with an appropriate emotion. Systemizing is the capacity to predict and to respond to the behavior of nonagentive deterministic systems by analyzing input-operation-output relations and inferring the rules that govern such systems. At a population level, females are stronger empathizers and males are stronger systemizers. The "extreme male brain" theory posits that autism represents an extreme of the male pattern (impaired empathizing and enhanced systemizing). Here we suggest that specific aspects of autistic neuroanatomy may also be extremes of typical male neuroanatomy.

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Sex differences in the brain : Implications for explaining autism

To determine whether a sex difference exists in the production of hippocampal cells during adulthood, we examined proliferating cells and their progeny in adult rats using the thymidine analog bromodeoxyuridine (BrdU) combined with immunohistochemistry for markers of neurons and glia. Additionally, to determine whether ovarian hormones affect cell proliferation, we examined the numbers of BrdU-labeled cells at different estrous cycle stages and after ovarian steroid manipulation. Stereological analyses of the numbers of BrdU-labeled cells revealed that females produced more cells than males in the dentate gyrus but not in the subventricular zone. The production of new hippocampal cells in females appears to be affected by ovarian hormone levels; ovariectomy diminished the number of BrdU-labeled cells, an effect reversed by estrogen replacement. A natural fluctuation in cell proliferation was also noted; females produced more cells during proestrus (when estrogen levels are highest) compared with estrus and diestrus. Many of these cells acquired neuronal characteristics, including the formation of dendrites and expression of Turned-On-After-Division 64 kDa, a marker of immature granule neurons, and the calcium-binding protein calbindin, a marker of mature granule neurons. However, examination of the numbers of pyknotic cells and the numbers of BrdU-labeled cells at longer survival times revealed that many new cells in the dentate gyrus eventually degenerate. Consistently the number of labeled cells in females is no longer higher than that observed in males by 2 weeks after the last BrdU injection. These findings suggest that estrogen-enhanced cell proliferation during proestrus results in more immature neurons in the hippocampal formation of females compared with males and present the possibility that these new cells exert an important influence on hippocampal function.

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Estrogen stimulates a transient increase in the number of new neurons in the dentate gyrus of the adult female rat.

https://digital.csic.es/bitstream/10261/72251/1/GarciaSegura%2c2001%2cProgressNeurobiol.%2c63%2c29-.pdf

Neuroprotection by estradiol.

Progesterone facilitates cognitive recovery and reduces secondary neuronal loss caused by cortical contusion injury in male rats.

The gonadal hormone, progesterone, has been shown to have neuroprotective effects in injured nervous system, including the severity of postinjury cerebral edema. Progesterone’s attenuation of edema is accompanied by a sparing of neurons from secondary neuronal death and with improvements in cognitive outcome. In addition, we recently reported that postinjury blood-brain barrier (BBB) leakage, as measured by albumin immunostaining, was significantly lower in progesteronetreated than in nontreated rats, supporting a possible protective action of progesterone on the BBB. Because lipid membrane peroxidation is a major contributor to BBB breakdown, we hypothesized that progesterone limits this free radical-induced damage. An antioxidant action, neuroprotective in itself, would also account for progesterone’s effects on the BBB, edema, and cell survival after traumatic brain injury. To test progesterone’s possible antiperoxidation ef-fect, we compared brain levels of 8-isoprostaglandin F2α (8-isoPGF2α), a marker of lipid peroxidation, 24, 48, and 72 h after cortical contusion in male rats treated with either progesterone or the oil vehicle. The brains of progesteronetreated rats contained approximately one-third of the 8-isoPGF2α found in oil-treated rats. These data suggest progesterone has antioxidant effects and support its potential as a treatment for brain injury.

Robin L. Roof

Papers

Progesterone facilitates cognitive recovery and reduces secondary neuronal loss caused by cortical contusion injury in male rats.

Progesterone protects against lipid peroxidation following traumatic brain injury in rats

Gender influences outcome of brain injury: progesterone plays a protective role

Progesterone Rapidly Decreases Brain Edema: Treatment Delayed up to 24 Hours Is Still Effective

Gender differences in Morris water maze performance depend on task parameters.