Risto Kauppinen - Academia.edu (original) (raw)

Papers by Risto Kauppinen

Synapse, 2000

It has been suggested that the increased production of endogenous BDNF after brain insults suppor... more It has been suggested that the increased production of endogenous BDNF after brain insults supports the survival of injured neurons and limits the spread of the damage. In order to test this hypothesis experimentally, we have produced transgenic mouse lines that overexpress the dominant-negative truncated splice variant of BDNF receptor trkB (trkB.T1) in postnatal cortical and hippocampal neurons. When these mice were exposed to transient focal cerebral ischemia by occluding the middle cerebral artery for 45 min and the damage was assessed 24 h later, transgenic mice had a significantly larger damage than wild-type littermates in the cerebral cortex (204 ؎ 32% of wild-type, P ‫؍‬ 0.02), but not in striatum, where the transgene is not expressed. Our results support the notion that endogenously expressed BDNF is neuroprotective and that BDNF signaling may have an important role in preventing brain damage after transient ischemia.

J Magn Reson, 2010

Magnetization transfer (MT) MRI and Z-spectroscopy are tools to study both water-macromolecule in... more Magnetization transfer (MT) MRI and Z-spectroscopy are tools to study both water-macromolecule interactions and pH-sensitive exchange dynamics between water and the protons of mobile chemical groups within these macromolecules. Both rely on saturation of frequencies offset from water and observation of the on-resonance water signal. In this work, an RF saturation method called Z-spectroscopy with Alternating-Phase Irradiation (ZAPI) is introduced. Based on the T(2)-selectivity of the irradiation pulse, ZAPI can be used to separate the different contributions to a Z-spectrum, as well as to study the T(2) distribution of the macromolecules contributing to the MT signal. ZAPI can be run at resonance for water and with low power, thus minimizing problems with specific absorption rate (SAR) limits in clinical applications. In this paper, physical and practical aspects of ZAPI are discussed and the sequence is applied in vitro to sample systems and in vivo to rat head to demonstrate the method.

The present study was undertaken to explore the possible neuroprotective effect of the selective ... more The present study was undertaken to explore the possible neuroprotective effect of the selective a -adrenoceptor agonist, 2 ) Corresponding author. A.I. Virtanen

Brain Research, 1997

. Selegiline L-deprenyl has shown neuroprotective effects in a variety of degenerative processes.... more . Selegiline L-deprenyl has shown neuroprotective effects in a variety of degenerative processes. The present experiments were designed to test whether post-ischemia administered selegiline would alleviate delayed neuronal death of the gerbil hippocampal pyramidal cells following transient global ischemia. Common carotid arteries were occluded for 5 min. Saline or selegiline, 0.25 mgrkg s.c., was administered 2 h after the ischemia followed by a daily injection for either 3 or 7 days. After decapitation, the delayed death of the hippocampal CA1 pyramidal cells was assessed using Nissl-stained sections. In situ hybridization was used to reveal the expression of Ž hsp70 mRNA 1, 3 or 7 days after the ischemia. Animals treated with selegiline for 7 days showed significantly lower damage score scale . 0-3: 0, normal; 1, -10% of the neurons damaged; 2, 10-50% damaged; 3, ) 50% damaged compared to the saline-treated animals Ž . 1.73 " 0.18 and 2.41 " 0.16 mean " S.E.M., P s 0.0133 , respectively. A similar trend was found in animals after the 3-day treatment: Ž . 1.68 " 0.32 vs. 2.06 " 0.25 P ) 0.5 . The expression of hsp70 mRNA in the CA1 pyramidal cell layer was strong still 3 days after the ischemic insult but vanished by 7 days. Densitometric measurements using 14 C-plastic standards showed that the intensity of the CA1a Ž . hsp70 signal on the 3rd day correlated negatively to the cell-damage score r sy0.72, P -0.001 , suggesting that hsp70 does not serve as a quantitative marker for CA1 neuronal injury in this model. Instead, the hsp70 expression was associated with improved neuronal Ž . survival lasting often longer in selegiline-treated animals P ) 0.5 . The results show that a low dose of selegiline can alleviate the delayed hippocampal neuronal death in gerbils when administered 2 h after an ischemic insult.

Pharmacology & Toxicology, 2008

The present study investigated the effect of postischaemic infusion of an irreversible monoamine ... more The present study investigated the effect of postischaemic infusion of an irreversible monoamine oxidase B (MAO-B) inhibitor, l-deprenyl, an equipotent dose of a reversible MAO-B inhibitor, lazabemide, or 0.9% NaCl on infarct volumes following focal cerebral ischaemia in rats. The drug doses (0.3 mg/kg) were selected to induce selective MAO-B inhibition (45-55%), but not MAO-A inhibition. The infarct volumes in the cortex or in the striatum did not differ between the experimental groups 72 hr after transient occlusion of the middle cerebral artery, which suggests that during ischaemia/reperfusion, suppressed oxidative stress by partial MAO-B inhibition or MAO-B independent mechanisms such as induction of trophic factors, does not protect against ischaemia/reperfusion damage.

Magnetic Resonance in Medicine, 2005

Transverse relaxation in the rotating frame (T(2rho)) is the dominant relaxation mechanism during... more Transverse relaxation in the rotating frame (T(2rho)) is the dominant relaxation mechanism during an adiabatic Carr-Purcell (CP) spin-echo pulse sequence when no delays are used between pulses in the CP train. The exchange-induced and dipolar interaction contributions (T(2rho,ex) and T(2rho,dd)) depend on the modulation functions of the adiabatic pulses used. In this work adiabatic pulses having different modulation functions were utilized to generate T(2rho) contrast in images of the human occipital lobe at magnetic field of 4 T. T(2rho) time constants were measured using an adiabatic CP pulse sequence followed by an imaging readout. For these measurements, adiabatic full passage pulses of the hyperbolic secant HSn (n = 1 or 4) family having significantly different amplitude-and frequency-modulation functions were used with no time delays between pulses. A dynamic averaging (DA) mechanism (e.g., chemical exchange and diffusion in the locally different magnetic susceptibilities) alone was insufficient to fully describe differences in brain tissue water proton T(2rho) time constants. Measurements of the apparent relaxation time constants (T(2) (dagger)) of brain tissue water as a function of the time between centers of pulses (tau(cp)) at 4 and 7 T permitted separation of the DA contribution from that of dipolar relaxation. The methods presented assess T(2rho) relaxation influenced by DA in tissue and provide a means to generate T(2rho) contrast in MRI.

Magnetic Resonance in Medicine, 2001

The present study was designed to investigate whether T 2weighted signal changes obtained by micr... more The present study was designed to investigate whether T 2weighted signal changes obtained by microimaging of paraformaldehyde-fixed brain correlate with the histologically quantified damage in a model of status epilepticus (SE) induced by kainic acid in the rat. Animals were killed at several time points up to 8 weeks after a single intraperitoneal kainate (KA) injection (9 mg/kg). Perfusion-fixed brains were embedded in gelatin for MR microimaging at 9.4T. After the MRI analysis, the gelatin was removed and the brains were cryoprotected and processed for quantitative histology. Severity of neuronal damage and gliosis were assessed from thionin-stained serial sections.

Magnetic Resonance in Medicine, 2003

The ability of on-resonance T 1 (T 1 ) and off-resonance T 1 (T 1 off ) measurements to indicate ... more The ability of on-resonance T 1 (T 1 ) and off-resonance T 1 (T 1 off ) measurements to indicate acute cerebral ischemia in a rat model of transient middle cerebral artery (MCA) occlusion was investigated at 4.7 T. T 1 was determined with B 1 fields of 0.4, 0.8, and 1.6 G, and T 1 off with five offset frequencies (⌬) ranging from 0 -7.5 kHz at B 1 of 0.4 G, yielding effective B 1 (B eff ) from 0.4 to 1.8 G. Diffusion, T 1 , and T 2 were also quantified. Both T 1 and T 1 off acquired with ⌬ < 2.5 kHz showed positive contrast during the first hours of MCA occlusion in the ischemic tissue delineated by low diffusion. Interestingly, T 1 off contrast acquired with ⌬ > 2.5 kHz was clearly less sensitive to ischemic alterations, and developed with a delayed time course. This discrepancy is thought to be a consequence of the frequency dependency of cross-relaxation during irradiation with spin-lock pulses. Magn Reson Med 49: 172-176, 2003.

Magnetic Resonance Imaging, 2006

Characteristics of the blood-oxygenation-level-dependent (BOLD) functional magnetic resonance ima... more Characteristics of the blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal poststimulus undershoot in the visual cortex were studied at varying levels of arterial blood oxygen saturation ( Y sat ). Undershoot with an amplitude of À0.6F0.2% appeared after positive BOLD response (+1.7F0.5%) under control conditions. Cerebral blood volume (CBV), as determined with vascular-space-occupancy-dependent fMRI, increased by 26 -43% during the positive BOLD peak, but the CBV proceeded at baseline level during the BOLD poststimulus undershoot. Mild hypoxic hypoxia ( Y sat ranging from 0.82 to 0.89) had no effect on the amplitude or duration of poststimulus undershoot in activated BOLD pixels. Hypoxia did not influence CBV during the BOLD poststimulus undershoot. In contrast, the positive BOLD signal at the level of all activated pixels was smaller in hypoxia than in normoxia. The present results show that the BOLD poststimulus undershoot is not influenced by curtailed oxygen availability and that, during the undershoot, CBV is not different from resting state. D

Journal of Proteome Research, 2011

O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) is important in a number of biolog... more O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) is important in a number of biological processes and diseases including transcription, cell stress, diabetes, and neurodegeneration and may be a marker of tumor metastasis. Uridine diphospho-Nacetylglucosamine (UDP-GlcNAc), the donor molecule in O-GlcNAcylation, can be detected by 1 H nuclear magnetic resonance spectroscopy ( 1 H NMR), giving the potential to measure its level noninvasively, providing a novel biomarker of prognosis and treatment monitoring. In this in vitro metabonomic study, four brain cancer cell lines were exposed to cisplatin and studied for metabolic responses using 1 H NMR. The Alamar blue assay and DAPI staining were used to assess cell sensitivity to cisplatin treatment and to confirm cell death. It is shown that in the cisplatin responding cells, UDP-GlcNAc and uridine diphospho-N-acetylgalactosamine (UDP-GalNAc), in parallel with 1 H NMR detected lipids, increased with cisplatin exposure before or at the onset of the microscopic signs of evolving cell death. The changes in UDP-GlcNAc and UDP-GalNAc were not detected in the nonresponders. These glycosylated UDP compounds, the key substrates for glycosylation of proteins and lipids, are commonly implicated in cancer proliferation and malignant transformation. However, the present study mechanistically links UDP-GlcNAc and UDP-GalNAc to cancer cell death following chemotherapeutic treatment.

Journal of Cerebral Blood Flow & Metabolism, 2009

The rotating frame longitudinal relaxation magnetic resonance imaging (MRI) contrast, T 1q , obta... more The rotating frame longitudinal relaxation magnetic resonance imaging (MRI) contrast, T 1q , obtained with on-resonance continuous wave (CW) spin-lock field is a sensitive indicator of tissue changes associated with hyperacute stroke. Here, the rotating frame relaxation concept was extended by acquiring both T 1q and transverse rotating frame (T 2q ) MRI data using both CW and adiabatic hyperbolic secant (HSn; n = 1, 4, or 8) pulses in a rat stroke model of middle cerebral artery occlusion. The results show differences in the sensitivity of spin-lock T 1q and T 2q MRI to detect hyperacute ischemia. The most sensitive techniques were CW-T 1q and T 1q using HS4 or HS8 pulses. Fitting a two-pool exchange model to the T 1q and T 2q MRI data acquired from the infarcting brain indicated time-dependent increase in free water fraction, decrease in the correlation time of water fraction associated with macromolecules, and increase in the exchange correlation time. These findings are consistent with known pathology in acute stroke, including vasogenic edema, destructive processes, and tissue acidification. Our results show that the sensitivity of the spinlock MRI contrast in vivo can be modified using different spin-lock preparation blocks, and that physicochemical models of the rotating frame relaxation may provide insight into progression of ischemia in vivo.

Applied Magnetic Resonance, 2005

Abstraet. T t in the rotating frame (T~p) has been recently shown to be an early magnetic resonan... more Abstraet. T t in the rotating frame (T~p) has been recently shown to be an early magnetic resonance imaging index of ongoing pathology in vivo. Dispersion of T~p at a B~ range from 620 to 160500 rad/s was quantified in the rat brain to study the effects of ischaemia on T~p relaxation and to elude the role of physico-chemical mechanisms underlying the relaxation changes. The results show a biphasic effect of the dispersion of Rip (1/T~p) in ischaemic brain. In the low B I region (less than 5000 rad/s), an increase was detected, while at the high B~ end of the experiments, R~p was reduced. This was accompanied by a change in the fitted values describing the dispersion characteristics. Injection of a superparamagnetic contrast agent, AMI-227, before ischaemia shifted the R~p curve upwards by 4% but showed no effect on the shape of the R~p dispersion curve. The present results argue for a specific effect of endogenous susceptibility on cerebral R~p in the early moments of ischaemia due to a relaxation enhancement in the blood pool. Our results confirm that quantitative R~p dispersion nuclear magnetie resonance (NMR) improves the sensitivity of R~~ NMR to detect ischaemia in vivo. Simple empirical linear or exponential fits proved to be efficient ways to describe dispersion data in the limited B~ range, as more detailed models may not offer additional information in a physically relevant manner for complex systems, such as the brain.

Analytical Biochemistry, 2000

High-resolution magic angle spinning (MAS) 1 H NMR spectroscopy has been used to investigate the ... more High-resolution magic angle spinning (MAS) 1 H NMR spectroscopy has been used to investigate the biochemical composition of whole rat renal cortex and liver tissue samples. The effects of a number of sample preparation procedures and experimental variables have been investigated systematically in order to optimize spectral quality and maximize information recovery. These variables include the effects of changing the sample volume in the MAS rotor, snap-freezing the samples, and the effect of organ perfusion with deuterated saline solution prior to MAS NMR analysis. Also, the overall biochemical stability of liver and kidney tissue MAS NMR spectra was investigated under different temperature conditions. We demonstrate improved resolution and line shape of MAS NMR spectra obtained from small spherical tissue volume (12 l) rotor inserts compared to 65 l cylindrical samples directly inserted into the MAS rotors. D 2 O saline perfusion of the in situ afferent vascular tree of the tissue immediately postmortem also improves line shape in MAS NMR spectra. Snap-freezing resulted in increased signal intensities from ␣-amino acids (e.g., valine) in tissue together with decreases in renal osmolytes, such as myo-inositol. A decrease in triglyceride levels was observed in renal cortex following stasis on ice and in the MAS rotor (303 K for 4 h). This work indicates that different tissues have differential metabolic stabilities in 1 H MAS NMR experi-ments and that careful attention to sample preparation is required to minimize artifacts and maintain spectral quality.

Human brain mapping, Jan 18, 2015

Understanding how spatially remote brain regions interact to form functional brain networks, and ... more Understanding how spatially remote brain regions interact to form functional brain networks, and how these develop during the neonatal period, provides fundamental insights into normal brain development, and how mechanisms of brain disorder and recovery may function in the immature brain. A key imaging tool in characterising functional brain networks is examination of T2*-weighted fMRI signal during rest (resting state fMRI, rs-fMRI). The majority of rs-fMRI studies have concentrated on slow signal fluctuations occurring at <0.1 Hz, even though neuronal rhythms, and haemodynamic responses to these fluctuate more rapidly, and there is emerging evidence for crucial information about functional brain connectivity occurring more rapidly than these limits. The characterisation of higher frequency components has been limited by the sampling frequency achievable with standard T2* echoplanar imaging (EPI) sequences. We describe patterns of neonatal functional brain network connectivity d...

Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine, 2004

On-resonance longitudinal relaxation time in the rotating frame (T1rho) has been shown to provide... more On-resonance longitudinal relaxation time in the rotating frame (T1rho) has been shown to provide unique information during the early minutes of acute stroke. In the present study, the contributions of the different relaxation mechanisms to on-resonance T1rho relaxation were assessed by determining relaxation rates (R1rho) in both protein phantoms and in rat brain at 2.35, 4.7, and 9.4 T. Similar to transverse relaxation rate (R2), R1rho increased substantially with increasing magnetic field strength (B0). The B0 dependence was more pronounced at weak spin-lock fields. In contrast to R1rho, longitudinal relaxation rate (R1) decreased as a function of increasing B0 field. The present data argue that dipole-dipole interaction forms only one pathway for T1rho relaxation and the contributions from other physicochemical factors need to be considered.