Repeat traumatic brain injury in the developing brain

The Center for Disease Control estimates that there are 1.7 million brain injuries in the US each year with 51% of these injuries occurring during periods of cerebral development. Among this population there is a growing population of individuals with repeat traumatic brain injury (RTBI). While the exact incidence is unknown, estimates range from 5.6 to 36% of the TBI population. This review summarizes the clinical problems/challenges and experimental research models that currently exist. It is intended to reveal the critical areas that need to be addressed so that age-relevant clinical management guidelines can be established to protect this population.     

The features of the brain immune system in brain neoplasms

Examining responses of the local immune system of the brain in neurocancer patients suggests that the immune system is involved in the neuroimmune interaction of both physiological and pathological conditions in the central nervous system (CNS). The setting off the local immune system of the brain is of functional nature, similar to functional analogy with the local system of the mucosae. By functional analogy, the aggregate of immune responses in the nervous tissue and cerebrospinal fluid should be called local and the system that includes these responses should named the local immune system of the brain. Due to the fact that nervous, endocrine, and immune regulatory pathways intersect in the CNS (hypothalamus), it is expedient to call this aggregate of defensive factors and mechanisms in CNS more broadly--the neuroimmune system.     

Laboratory of Caribbean brain research organization in the decade of the brain midpoint

CARIBRO was founded in response to the United Nations declaration that the 1990s be designated the Decade of the Brain. The Program of Action is:

1. Annual meetings;
2. Training courses of the Caribbean School of Neurosciences;
3. Network scientific programs;
4. Fellowship programs; and
5. Dissemination of information on neuroscience.

In the same program, a CARIBRO Laboratory was created in one of the Medical Faculties of Havana with the aim to teach students from the Caribbean in neuroscience research. As part of this program, we have been working in lateralized motor functions. Preliminary results in rats show that reaching acquisition allows classification of the animals as right-handed (40%), left-handed (40%), and ambidextrous (20%). Electrolytic lesion of caudate nucleus or amygdala impairs lateralized response. Contralateral lesions increase reaching attempts. Ipsilateral lesions to the preferred forepaw do not affect the reaction. The results remain the same 10, 20, and 90 d after the interference. Pharmacological experiments showed that trihexiphenidil (0.1 mg/kg ip) induced handedness reversion in 50% of the animals, whereas haloperidol (1 mg/kg ip) produced immobility, tremor, and autonomic symptoms. This effect remained the same in young as well as in old animals. We are also working on mathematical modelation. In this sense, preliminary reports about a model for synaptic modification in the framework of the Fukushima hypothesis is discussed.     

Laboratory of Caribbean brain research organization in the decade of the brain midpoint

CARIBRO was founded in response to the United Nations declaration that the 1990s be designated the Decade of the Brain. The Program of Action is:

1. Annual meetings;
2. Training courses of the Caribbean School of Neurosciences;
3. Network scientific programs;
4. Fellowship programs; and
5. Dissemination of information on neuroscience.

In the same program, a CARIBRO Laboratory was created in one of the Medical Faculties of Havana with the aim to teach students from the Caribbean in neuroscience research. As part of this program, we have been working in lateralized motor functions. Preliminary results in rats show that reaching acquisition allows classification of the animals as right-handed (40%), left-handed (40%), and ambidextrous (20%). Electrolytic lesion of caudate nucleus or amygdala impairs lateralized response. Contralateral lesions increase reaching attempts. Ipsilateral lesions to the preferred forepaw do not affect the reaction. The results remain the same 10, 20, and 90 d after the interference. Pharmacological experiments showed that trihexiphenidil (0.1 mg/kg ip) induced handedness reversion in 50% of the animals, whereas haloperidol (1 mg/kg ip) produced immobility, tremor, and autonomic symptoms. This effect remained the same in young as well as in old animals. We are also working on mathematical modelation. In this sense, preliminary reports about a model for synaptic modification in the framework of the Fukushima hypothesis is discussed.     

Neurofibromin in the brain

Neurofibromatosis 1 is one of the most common autosomal dominant disorders affecting the nervous system. Individuals with neurofibromatosis 1 present with abnormalities of both astrocytes and neurons that result from reduced or absent expression of the NF1 gene product neurofibromin. Impaired neurofibromin function in these nervous system cells contributes to the development of astrocytomas, learning disabilities, and radiographic abnormalities of the brain. With the identification of NF1, significant advances have begun to unlock some of the mysteries that surround the molecular pathogenesis of neurofibromatosis 1-associated brain abnormalities. With continued advances in our basic understanding of NF1 function, future targeted therapies for neurofibromatosis 1-associated central nervous system abnormalities can be developed.     

Shadows in the brain

The aims of the present study were to investigate whether the processing of an object shadow occurs implicitly, that is without conscious awareness, and where physically within the human brain shadows are processed. Here we present neurological evidence, obtained from studies of brain-injured patients with visual neglect, that shadows are implicitly processed and that this processing may take place within the temporal lobe. Neglect patients with lesions that do not involve the right temporal lobe were still able to process shadows to optimize object shape perception. In contrast, shadow processing was not found to be as efficient in neglect patients with lesions that involve the right temporal lobe.     

Discovering the individual brain: brain stimulation in psychiatry

European Archives of Psychiatry and Clinical Neuroscience -     

Peptides in the brain

More than 25 biologically active peptides have been identified in the CNS. They are involved in the regulation of complex cerebral functions such as sleep, ingestive and motor behavior, pain, cognition, emotions and mood. In view of the coexistence of peptides with classical transmitters in the same nerve endings of some central neurons the concept of cotransmission has been recently developed. The intervention of peptides in transmission and cotransmission processes opens very stimulating ways of research in the field of neurology and psychiatry.     

Neuropeptides in the brain

In recent years, there has been a remarkable increase in the identification of neuropeptides. These peptides have become known as neuropeptides, as they have been identified within neuronal structures and frequently localised to nerve terminals. Classification of newly discovered peptides is attempted according to function or structure. Although the role of the hypothalamic releasing factors is readily appreciated, the functional significance of the remaining neuropeptides is often not easily determined. However, these peptide appear to interact with conventional transmitters and may be implicated in neuropathology.     

Phenobarbital modifies seizure-related brain injury in the developing brain

To investigate the potential role of drug therapy in preventing or exacerbating seizure-related brain injury in the prepubescent brain, we administered kainic acid to rats at postnatal day 35. Therapy with daily phenobarbital was started directly before or 1 day after kainic acid was administered, and was continued through postnatal day 153. Rats receiving phenobarbital had therapeutic concentrations during most of the 24-hour dosing period, but also experienced supratherapeutic peak concentrations. The animals were subsequently tested using the water maze (a measure of visuospatial memory), open field (a measure of activity level), and handling tests (a measure of emotionality). The frequency of spontaneous recurrent seizures was monitored during and after phenobarbital therapy. Kainic acid resulted in status epilepticus on postnatal day 35 in all the rats that received it but those receiving phenobarbital first manifested a shorter and less severe status epilepticus as compared to the rats given kainic acid alone. Rats starting phenobarbital immediately before kainic acid was administered did not differ from control rats on behavioral testing and had no subsequent spontaneous recurrent seizures and no histological lesions. Rats receiving kainic acid alone performed significantly poorer than did control rats in the water maze, were more aggressive, had histological lesions, and manifested spontaneous recurrent seizures. As compared to the group treated only with kainic acid, rats receiving kainic acid followed by phenobarbital at postnatal days 36 to 153 manifested similar aggressiveness and histological lesions, similar frequency of spontaneous recurrent seizures after phenobarbital taper, and even greater disturbances in memory, learning, and activity level. These results demonstrate that kainic acid–related injury can be prevented by a medication working through inhibitory mechanisms; that structural and functional damage in the prepubescent brain can be prevented through strategically timed pharmacotherapy; and that treatment of spontaneous recurrent seizures alone with daily exposure to phenobarbital does not decrease, and may actually exacerbate, damage in the kainic acid model.     

Mechanisms of angiogenesis in the brain

Brain angiogenesis is a tightly controlled process that is regulated by neuroectodermal derived growth factors that bind to tyrosine kinase receptors expressed on endothelial cells. In the rat brain, angiogenesis is complete around postnatal day 20, but endothelial cells can proliferate in the adult brain under pathological conditions such as hypoxia/ischemia and brain tumor growth. Current evidence suggests that physiological angiogenesis in the brain is regulated by similar mechanisms as pathological angiogenesis induced by tumors or by hypoxia/ischemia. The hypoxia-inducible endothelial cell mitogen and vascular permeability factor, vascular endothelial growth factor (VEGF) appears to play a pivotal role in most of these processes. VEGF is expressed when angiogenesis is high, as in embryonic neuroectoderm, in glioblastomas and around infarcts, but is expressed at low levels when angiogenesis is absent, as in adult neuroectoderm. Since growth factors such as VEGF and angiopoietins and their receptors appear to be necessary for angiogenesis, targeting of growth factor/receptor pathways for angiogenesis-dependent diseases such as glioblastoma might be useful for therapy. Several compounds, including anti-VEGF antibodies and VEGFR-2 inhibitors are currently in clinical trial. On the other hand, induction of angiogenesis by growth factors (pro-angiogenesis) might prove to be a rational therapy for patients with stroke.     

Images of the brain in psychiatry

In psychiatry, the use of computer-based techniques for constructing images of the brain is relatively recent. Nevertheless, findings that have resulted from their use thus far might provide us with a new perspective in the understanding of mental illness. They raise the possibility that many of the disorders, previously understood primarily in terms of psychosocial factors, are associated with specific abnormalities of brain structure and/or function. Although terms such as NMR, BEAM, RCBF, SPECT and PET are increasingly found in medical and psychiatric journals, few people understand in simple terms the principles on which these techniques are based. In this article the techniques used for constructing images of brain structure and function are explained, and an overview of the findings in psychiatric disorders is presented.