Resting-state functional magnetic resonance imaging (rsfMRI) is a translational imaging method with great potential in several neurobiologic applications. Most preclinical rsfMRI studies are performed in anesthetized animals, but the confounding effects of anesthesia on the measured functional connectivity (FC) are poorly understood. Therefore, we measured FC under six commonly used anesthesia protocols and compared the findings with data obtained from awake rats. The results demonstrated that each anesthesia protocol uniquely modulated FC. Connectivity patterns obtained under propofol and urethane anesthesia were most similar to that observed in awake rats. FC patterns in the α-chloralose and isoflurane-medetomidine combination groups had moderate to good correspondence with that in the awake group. The FC patterns in the isoflurane and medetomidine groups differed most from that in the awake rats. These results can be directly exploited in rsfMRI study designs to improve the data quality, comparability, and interpretation.

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One of the cardinal pathologic features of Alzheimer's disease (AD) is the formation of senile, or amyloid, plaques. Transgenic mice have been developed that express one or more of the genes responsible for familial AD in humans. Doubly transgenic mice develop "human-like" plaques, providing a mechanism to study amyloid plaque biology in a controlled manner. Imaging of labeled plaques has been accomplished with other modalities, but only MRI has sufficient spatial and contrast resolution to visualize individual plaques noninvasively. Methods to optimize visualization of plaques in vivo in transgenic mice at 9.4 T using a spin echo sequence based on adiabatic pulses are described. Preliminary results indicate that a spin echo acquisition more accurately reflects plaque size, while a T 2 * weighted gradient echo sequence reflects plaque iron content, not plaque size. In vivo MRI-ex vivo MRI-in vitro histologic correlations are provided. Histologically verified plaques as small as 50 m in diameter were visualized in living animals. To our knowledge this work represents the first demonstration of noninvasive in vivo visualization of individual AD plaques without the use of a contrast agent.

The amide proton transfer ratio (APTR) from the asymmetry of the Z-spectrum was determined in rat brain tissue during and after unilateral middle cerebral artery occlusion (MCAo). Cerebral lactate (Lac) as determined by

The impact of brain imaging on the assessment of tissue status is likely to increase with the advent of treatment methods for acute cerebral ischemia. Multimodal magnetic resonance imaging (MRI) demonstrates potential for selecting stroke therapy patients by identifying the presence of acute ischemia, delineating the perfusion defect, and excluding hemorrhage. Yet, the identification of tissue subject to reversible or irreversible ischemia has proven to be difficult. Here, the authors show that T1 relaxation time in the rotating frame, so-called T1rho, serves as a sensitive MRI indicator of cerebral ischemia in the rat. The T1rho prolongs within minutes after a drop in the CBF of less than 22 mL 100 g(-1) min(-1). Dependence of T1rho on spin-lock amplitude, termed as T1rho dispersion, increases by approximately 20% on middle cerebral artery (MCA) occlusion, comparable with the magnitude of diffusion reduction. The T1rho dispersion change dynamically increases to be 38% +/- 10% by the first 60 minutes of ischemia in the brain region destined to develop infarction. Following reperfusion after 45 minutes of MCA occlusion, the tissue with elevated T1rho dispersion (yet normal diffusion) develops severe histologically verified neuronal damage; thus, the former parameter unveils an irreversible condition earlier than currently available MRI methods. The T1rho dispersion as a novel MRI index of cerebral ischemia may be useful in determination of the therapeutic window for acute ischemic stroke.

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Summary: Epileptogenesis refers to a phenomenon in which the brain undergoes molecular and cellular alterations after a brain-damaging insult, which increase its excitability and eventually lead to the occurrence of recurrent spontaneous seizures. Common epileptogenic factors include traumatic brain injury (TBI), stroke, and cerebral infections. Only a subpopulation of patients with any of these brain insults, however, will develop epilepsy. Thus, there are two great challenges: (1) identifying patients at risk, and (2) preventing and/or modifying the epileptogenic process. Target identification for antiepileptogenic treatments is difficult in humans because patients undergoing epileptogenesis cannot currently be identified. Animal models of epileptogenesis are therefore necessary for scientific progress. Recent advances in the development of experimental models of epileptogenesis have provided tools to investigate the molecular and cellular alterations and their temporal appearance, as well as the epilepsy phenotype after various clinically relevant epileptogenic etiologies, including TBI and stroke. Studying these models will lead to answers to critical questions such as: Do the molecular mechanisms of epileptogenesis depend on the etiology? Is the spectrum of network alterations during epileptogenesis the same after various clinically relevant etiologies? Is the temporal progression of epileptogenesis similar? Work is ongoing, and answers to these questions will facilitate the identification of molecular targets for antiepileptogenic treatments, the design of treatment paradigms, and the determination of whether data from one etiology can be extrapolated to another. Key Words: Endothelin-1-Gene arrayLateral fluid-percussion injury-Magnetic resonance imagingPhotothrombotic stroke-Traumatic brain injury-Video-EEG monitoring.According to the World Health Organization, approximately 0.8% (50 million) of the world population has epilepsy (available from http://www.who.int/ mediacentre/factsheets/fs165/en/). Epilepsies can be divided into three major categories based on etiology: idiopathic, symptomatic, and presumed symptomatic (previously called "cryptogenic") (Engel, 2001). In idiopathic epilepsies, genetic factors causing, for example, channelopathies, are presumed to have a major causative role in the development of seizures. In symptomatic epilepsies, there is an identifiable lesion in the brain that triggers seizures. The lesion can be a genetically programmed cellular alteration like neuronal migration disorder in cortex or an acquired lesion like traumatic brain injury (TBI) or stroke. Presumed symptomatic epilepsies are those most likely to be symptomatic, but the lesions cannot be identified using currently available methods (Engel, 2001).

SUMMARYA large number of animal models of traumatic brain injury (TBI) are already available for studies on mechanisms and experimental treatments of TBI. Immediate and early seizures have been described in many of these models with focal or mixed type (both gray and white matter damage) injury. Recent long-term video-electroencephalography (EEG) monitoring studies have demonstrated that TBI produced by lateral fluid-percussion injury in rats results in the development of late seizures, that is, epilepsy. These animals develop hippocampal alterations that are well described in status epilepticus-induced spontaneous seizure models and human posttraumatic epilepsy (PTE). In addition, these rats have damage ipsilaterally in the cortical injury site and thalamus. Although studies in the trauma field provide a large amount of information about the molecular and cellular alterations corresponding to the immediate and early phases of PTE, chronic studies relevant to the epileptogenesis phase are sparse. Moreover, despite the multiple preclinical pharmacologic and cell therapy trials, there is no information available describing whether these therapeutic approaches aimed at improving posttraumatic recovery would also affect the development of lowered seizure threshold and epilepsy. To make progress, there is an obvious need for information exchange between the trauma and epilepsy fields. In addition, the inclusion of epilepsy as an outcome measure in preclinical trials aiming at improving somatomotor and cognitive recovery after TBI would provide valuable information about possible new avenues for antiepileptogenic interventions and disease modification after TBI.