Transport characteristics of guanidino compounds at the blood-brain barrier and blood-cerebrospinal fluid barrier: relevance to neural disorders

Guanidino compounds (GCs), such as creatine, phosphocreatine, guanidinoacetic acid, creatinine, methylguanidine, guanidinosuccinic acid, γ-guanidinobutyric acid, β-guanidinopropionic acid, guanidinoethane sulfonic acid and α-guanidinoglutaric acid, are present in the mammalian brain. Although creatine and phosphocreatine play important roles in energy homeostasis in the brain, accumulation of GCs may induce epileptic discharges and convulsions. This review focuses on how physiologically important and/or neurotoxic GCs are distributed in the brain under physiological and pathological conditions. Transporters for GCs at the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB) have emerged as substantial contributors to GCs distribution in the brain. Creatine transporter (CRT/solute carrier (SLC) 6A8) expressed at the BBB regulates creatine concentration in the brain, and represents a major pathway for supply of creatine from the circulating blood to the brain. CRT may be a key factor facilitating blood-to-brain guanidinoacetate transport in patients deficient in S-adenosylmethionine:guanidinoacetate N-methyltransferase, the creatine biosynthetic enzyme, resulting in cerebral accumulation of guanidinoacetate. CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF. Interestingly, BBB efflux transport of GCs, including guanidinoacetate and creatinine, is negligible, though the BBB has a variety of efflux transport systems for synthetic precursors of GCs, such as amino acids and neurotransmitters. Instead, the BCSFB functions as a major cerebral clearance system for GCs. In conclusion, transport of GCs at the BBB and BCSFB appears to be the key determinant of the cerebral levels of GCs, and changes in the transport characteristics may cause the abnormal distribution of GCs in the brain seen in patients with certain neurological disorders

Dynamic process of family burden in dementia caregiving: a new field for psychotherapeutic interventions

Families caring for a patient with dementia are prone to significant physical, psychological and social stress. It is now well established that the caregiver burden does not only negatively affect the caregiver's physical and mental health, but is also associated with an increase in behavioural and psychiatric symptoms of dementia. Burden determinants include the quality of the relationship between the patient and caregiver; patient variables, such as the need to manage the behavioural and psychological symptoms of dementia; and also caregiver variables, such as the satisfaction of caring, demographic characteristics and societal roles. The standardised assessment of interventions for caregivers in dementia care remains a difficult task. In recent years, family interventions that focus on the process of burden itself in relation to the caregiver's subjective experience of personal growth and enrichment have been proposed. This new approach is based on the identification of tasks and challenges faced by family members throughout the different stages of the disease. In this context, brief crisis interventions transform periods of disorganisation experienced by the family into opportunities for change, whereas rehabilitation interventions developed by professional caring networks offer a continuous assessment and advice to the family. This article provides a critical review of the consequences and determinants of caregiver burden in dementia care with special reference to the emerging notion of the caregiver's subjective experience in the context of family processes. (PsycINFO Database Record (c) 2006 APA, all rights reserved) (journal abstract