The apparent diffusion coefficient does not reflect cytotoxic edema on the uninjured side after traumatic brain injury

After traumatic brain injury, vasogenic and cytotoxic edema appear sequentially on the involved side. Neuroimaging investigations of edema on the injured side have employed apparent diffusion coefficient measurements in diffusion tensor imaging. We investigated the changes occurring on the injured and uninjured sides using diffusion tensor imaging/apparent diffusion coefficient and histological samples in rats. We found that, on the injured side, that vasogenic edema appeared at 1 hour and intracellular edema appeared at 3 hours. Mixed edema was observed at 6 hours, worsening until 12–24 hours post-injury. Simultaneously, microglial cells proliferated at the trauma site. Apparent diffusion coefficient values increased at 1 hour, decreased at 6 hours, and increased at 12 hours. The uninjured side showed no significant pathological change at 1 hour after injury. Cytotoxic edema appeared at 3 hours, and vasogenic edema was visible at 6 hours. Cytotoxic edema persisted, but vasogenic edema tended to decrease after 12–24 hours. Despite this complex edema pattern on the uninjured side with associated pathologic changes, no significant change in apparent diffusion coefficient values was detected over the first 24 hours. Apparent diffusion coefficient values accurately detected the changes on the injured side, but did not detect the changes on the uninjured side, giving a false-negative result.

Aquaporin-4 gene silencing protects injured neurons after early cerebral infarction

Aquaporin-4 regulates water molecule channels and is important in tissue regulation and water transportation in the brain. Upregulation of aquaporin-4 expression is closely related to cellular edema after early cerebral infarction. Cellular edema and aquaporin-4 expression can be determined by measuring cerebral infarct area and apparent diffusion coefficient using diffusion-weighted imaging（DWI）. We examined the effects of silencing aquaporin-4 on cerebral infarction. Rat models of cerebral infarction were established by occlusion of the right middle cerebral artery and si RNA-aquaporin-4 was immediately injected via the right basal ganglia. In control animals, the area of high signal intensity and relative apparent diffusion coefficient value on T2-weighted imaging（T2WI） and DWI gradually increased within 0.5–6 hours after cerebral infarction. After aquaporin-4 gene silencing, the area of high signal intensity on T2 WI and DWI reduced, relative apparent diffusion coefficient value was increased, and cellular edema was obviously alleviated. At 6 hours after cerebral infarction, the apparent diffusion coefficient value was similar between treatment and model groups, but angioedema was still obvious in the treatment group. These results indicate that aquaporin-4 gene silencing can effectively relieve cellular edema after early cerebral infarction; and when conducted accurately and on time, the diffusion coefficient value and the area of high signal intensity on T2 WI and DWI can reflect therapeutic effects of aquaporin-4 gene silencing on cellular edema.

Mouse cerebellar Purkinje cell damage induced by diphenylhydantoin acute intoxication

Twenty one days old Swiss albino mice that received diphenylhydantoin(25 mg/kg,i.p.,daily for 15 days)progressively developed gait alterations,changes of behavior and cerebellar ataxia.Cerebellar slices were processed by conventional transmission electron microscopy.The body of Purkinje cells exhibited fragmented limiting plasma membranes,dilated nuclear envelopes,swelling and disassembly of nuclear pores,enlargement of rough and smooth endoplasmic reticulum and a notable detachment of membrane associated ribosomes,to-gether with distorted vacuoles of smooth endoplasmic reticulum,bizarre shaped and swollen mitochondria with dilated cristae,as well as disrupted limiting lysosomal membranes.Degenerated axosomatic synapses apparently corresponding to basket cell axonal endings were recognized.Degenerated Purkinje cell axon initial segments exhibited vacuolar degeneration of myelin sheath,dilated axoplasmic tubular bundles,fragmented axonal mem-branes,swollen mitochondria,and disassembly of cytoskeletal structures.Some edematous and clear secondary and tertiary dendrites exhibited areas of dilated cisterns of smooth endoplasmic reticulum,clear and dark mul-tivesicular bodies,and coated vesicles.Other dendritic ramifications exhibited an electron dense dendroplasm.Degenerated and large climbing fiber endings were observed making axodendritic synapses with edematous Purkinje dendrites.These presynaptic endings appeared depleted or containing few synaptic vesicles.These syn-apses did not exhibit pre-and postsynaptic densities.At the molecular layer,the edematous synaptic varicosities of parallel fibers containing pleomorphic synaptic vesicles and dense extravesicular substance were observed making asymmetric synaptic contacts with swollen Purkinje dendritic spines.These findings are postulated as pathogenic mechanisms of mouse cerebellar ataxia.