Krishnan Sriram

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Carbon nanotubes (CNT) come in a variety of types, but one of the most common forms is multi-walled carbon nanotubes (MWCNT). MWCNT have potential applications in many diverse commercial processes, and thus human exposures are considered to be likely. In order to investigate the pulmonary toxicity of MWCNT, we conducted an in vivo dose-response and time(More)
Activated microglia are implicated in the pathogenesis of disease-, trauma- and toxicant-induced damage to the CNS, and strategies to modulate microglial activation are gaining impetus. A novel action of the tetracycline derivative minocycline is the ability to inhibit inflammation and free radical formation, factors that influence microglial activation.(More)
The pathogenic mechanisms underlying idiopathic Parkinson's disease (PD) remain enigmatic. Recent findings suggest that inflammatory processes are associated with several neurodegenerative disorders, including PD. Enhanced expression of the proinflammatory cytokine, tumor necrosis factor (TNF)-alpha, has been found in association with glial cells in the(More)
Proinflammatory cytokines and chemokines have been implicated in the pathogenesis of several neurological and neurodegenerative disorders. Prominent among such factors is the pleiotropic cytokine, tumor necrosis factor (TNF)-alpha. Under normal physiological conditions, TNF-alpha orchestrates a diverse array of functions involved in immune surveillance and(More)
Reactive gliosis is a hallmark of disease-, trauma-, and chemical-induced damage to the central nervous system. The signaling pathways associated with this response to neural injury remain to be elucidated, but recent evidence implicates the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway. Here, we used the known(More)
A variety of '-omic' technologies are being increasingly applied in preclinical safety assessments. Such approaches, however, have not been implemented in neurotoxicity safety evaluations. Current regulatory guidelines for assessing neurotoxicity emphasise reliance on traditional histopathological stains and behavioural testing batteries. Although these(More)
Obesity is a major risk factor associated with a variety of human disorders. While its involvement in disorders such as diabetes, coronary heart disease and cancer have been well characterized, it remains to be determined if obesity has a detrimental effect on the nervous system. To address this issue we determined whether obesity serves as a risk factor(More)
Enhanced expression of tumor necrosis factor (TNF) -alpha, is associated with the neuropathological effects underlying disease-, trauma- and chemically induced neurodegeneration. Previously, we have shown that deficiency of TNF receptors protects against MPTP-induced striatal dopaminergic neurotoxicity, findings suggestive of a role for TNF-alpha in(More)
This study investigated the in vivo pulmonary toxicity of inhaled multi-walled carbon nanotubes (MWCNT). Mice-inhaled aerosolized MWCNT (10 mg/m³, 5 h/day) for 2, 4, 8 or 12 days. MWCNT lung burden was linearly related to exposure duration. MWCNT-induced pulmonary inflammation was assessed by determining whole lung lavage (WLL) polymorphonuclear leukocytes(More)
Human ingestion of "chickling peas" from the plant Lathyrus sativus, which contains an excitatory amino acid, L-BOAA (L-beta-N-oxalylamino-L-alanine), leads to a progressive corticospinal neurodegenerative disorder, neurolathyrism. Exposure to L-BOAA, but not its optical enantiomer D-BOAA, causes mitochondrial dysfunction as evidenced by loss of complex I(More)